Decreased interstitial glucose and transmural gradient in lactate during ischemia

Summary The purpose of this investigation was to assess the effects of ischemia and reperfusion on the transmural levels of glucose and lactate in the interstitium in 11 open-chest swine. Microdialysis probes were used to estimate changes in interstitial metabolities across the ventricular wall. Probes were placed in the subepicardium and the subendocardium of the left anterior descending (LAD) coronary artery perfusion bed and in the midmyocardium of the circumflex (CFX) perfusion bed. The LAD coronary artery was cannulated and perfused with blood from the femoral artery through an extracorporal perfusion circuit. Ischemia was induced in the LAD perfusion bed by reducing the flow of the LAD perfusion pump by 60% for 50 min, and was followed by 30 min of reperfusion. Regional myocardial blood flow was assessed with fluorescent microspheres. Ischemia resulted in a transmural gradient in blood flow, with the most severe reduction in flow occurring in the subendocardium (p<0.05). We found a significant reduction in interstitial glucose in both the LAD subepicardium (1.26±0.24 mM) (p=0.0009) and subendocardium (0.89±0.21 mM) (p=0.0001) during ischemia compared to the aerobic (non-ischemic) period (1.97±0.25 mM, 2.03±0.29 mM for the subepicardium and subendocardium, respectively). This coincided with a significant reduction in glucose delivery (LAD pump flow^* arterial glucose) to the LAD perfusion bed during ischemia (54.5±8.5 mol/min) compared to aerobic values (182.1±25.3 mol/min) (p<0.05). Interstitial lactate levels were significantly increased during ischemia in the LAD subendocardium (3.39±0.46 mM) compared to the aerobic values (1.73±0.46 mM) (p<0.0029). A transmural gradient in interstitial lactate levels was observed during ischemia: this gradient was not seen during the aerobic period and was negated upon reperfusion. In conclusion, ischemia resulted in a decrease in interstitial glucose in both the LAD subepicardium and subendocardium, and an increase in interstitial lactate in the LAD subendocardium. Further, a transmural gradient in interstitial lactate levels was observed during ischemia, with the highest lactate values appearing in the subendocardium.     

The “jerky dystonic unsteady hand”: A delayed motor syndrome in posterior thalamic infarctions

We report the cases of three patients with a thalamic infarct in the territory of the posterior choroidal artery involving the posterior thalamic nuclei. These patients developed delayed complex hyperkinetic motor syndromes, associating ataxia, tremor, dystonia, myoclonus and chorea, which we call the jerky dystonic unsteady hand. One patient had a severe myoclonic and ataxicdystonic choreoathetosis; another showed a so-called rubral tremor (myoclonic ataxia with resting, action, and wing-beating tremor) with dystonia; and the third one had a dystonic and ataxic hand with intermittent mild action myoclonus. All of them had sensory dysfunction; two had also presented with a painful Dejérine-Roussy syndrome. All had CT or MRI-proven infarcts in the territory of the posterior cerebral artery involving the posterior choroidal territory with an abnormal signal in the posterior area of the thalamus (pulvinar nucleus) but sparing the other thalamic, subthalamic and midbrain structures. These delayed myoclonic complex hyperkinetic syndromes have not been reported before, and we did not observe them in other topographic forms of thalamic infarcts. They may thus represent a new entity of movement disorders due to lesions in the posterior thalamic nuclei, with specificity for posterior choroidal artery infarcts.     

Objective Pulse-Synchronous "Essential" Tinnitus due to Narrowing of the Transverse Dural Venous Sinus

Subjective tinnitus is a common problem with many etiologies. Objective tinnitus, in which the sound is perceived by both the patient and the examiner, is less common. Objective tinnitus of the vascular type, in which a pulse synchronous bruit is heard by an independent observer, is frequently related to an underlying arterial or arteriovenous malformation, most commonly a dural arteriovenous fistula (DAVF) involving the transverse and sigmoid sinuses. The remaining cases are usually termed "essential" vascular tinnitus, and are presumed to have a venous etiology. In these cases, the audible noise is generally assumed to be produced within the sino-jugular connection, or within an enlarged jugular bulb. We present four documented cases of objective pulse synchronous tinnitus due to focal narrowing (acquired and developmental) of the mid-portion of the transverse dural sinus. In all cases, a bruit was audible directly over a focal constriction in the sinus, demonstrated by cerebral angiography or direct catheter venography. In one case, selective venography revealed a distensible sinus narrowing, associated with a jet of contrast marking fast flow within a developmental sinus segmentation. In another case, a loud pulse synchronous bruit was heard directly over a focal transverse sinus stenosis, which was detected by angiography at the site of a vascular surgical clip. In this case, magnetic resonance (MR) falsely predicted sinus occlusion. In two other cases, an audible bruit was also heard directly overlying a narrowed transverse sinus, seen in the venous phase of angiography. Transverse sinus stenosis is an unappreciated cause of objective pulsatile tinnitus, and we believe that this mechanism may underlie many cases of "essential" or venous etiology tinnitus not otherwise anatomically explained. Non-invasive testing, computed tomography (CT) and MR and non-directed angiography may overlook it. Conventional catheter arteriography or venography should be performed in such cases, with attention to the dural sinuses, if other tests fail to define the anatomic basis of the audible bruit.     

A survey of teenage pregnant women and their male partners in the Grampian region

This paper describes an exploratory pilot study of the male partners of teenagers presenting for either termination of pregnancy (TOP) or antenatal care (ANC). Seventy-five teenage pregnant women were recruited into the study and were asked to complete a questionnaire. The results suggest that the male partners tended to be older than their teenage partners. Teenage pregnant women presenting for termination of pregnancy had statistically significant higher levels of education, compared to those presenting for antenatal care. An association was found between the women's decision to continue or not with the pregnancy and her chosen form of contraception. In the antenatal group, women tended to state that their male partner's indication of support had influenced their decision to continue with the pregnancy. In-depth research should be conducted on the male partners of teenage pregnant women if effective sex education interventions are to be developed.     

Simulation studies of optimum energies for DXA: dependence on tissue type, patient size and dose model

Dual-energy x-ray absorptiometry (DXA) is a well established technique for measuring bone mineral density (BMD). However, in recent years DXA is increasingly being used to measure body composition in terms of fat and fat-free mass. DXA scanners must also determine the soft tissue baseline value from soft-tissue-only regions adjacent to bone. The aim of this work is to determine, using computer simulations, the optimum x-ray energies for: a number of dose models, different tissues, i.e. bone mineral, average soft tissue, lean soft tissue and fat; and a range of anatomical sites and patient sizes. Three models for patient dose were evaluated: total beam energy, entrance exposure and absorbed dose calculated by Monte Carlo modelling. A range of tissue compositions and thicknesses were chosen to cover typical patient variations for the three sites: femoral neck, PA spine and lateral spine. In this work, the optimisation of the energies is based on: (1) the uncertainty that arises from the quantum statistical nature of the number of x-rays recorded by the detector, and (2) the radiation dose received by the patient. This study has deliberately not considered other parameters such as detector response, electronic noise, x-ray tube heat load etc, because these are technology dependent parameters, not ones that are inherent to the measuring technique. Optimisation of the energies is achieved by minimisation of the product of variance of density measurement and dose which is independent of the absolute intensities of the x-ray beams. The results obtained indicate that if solving for bone density, then Elow in the range 34 to 42 keV, Ehigh in the range 100 to 200 keV and incident intensity ratio (low energy/high energy) in the range 3 to 10 is a reasonable compromise for the normal range of patient sizes. The choice of energies is complicated by the fact that the DXA unit must also solve for fat and lean soft tissue in soft-tissue-only regions adjacent to the bone. In this case the ranges of energies suggested above are acceptable only for the average phantom. In extreme cases the variance-dose product can be up to 50 times higher than for the ideal energies.     

Increasing hamstring flexibility decreases lower extremity overuse injuries in military basic trainees

The purpose of this intervention study was to prove that increasing flexibility of the hamstring musculotendinous unit would decrease the number of lower extremity overuse injuries that occur in military infantry basic trainees. Two different companies going through basic training at the same time were used. Hamstring flexibility was checked at the beginning and at the end of the 13-week infantry basic training course. The control company (N = 148) proceeded through normal basic training. The intervention company (N = 150) followed the same program but added three hamstring stretching sessions to their already scheduled fitness program. All subsequent lower extremity overuse injuries were recorded through the troop medical clinic. Hamstring flexibility increased significantly in the intervention group compared with the control group. The number of injuries was also significantly lower in the intervention group. Forty-three injuries occurred in the control group for an incidence rate of 29.1%, compared with 25 injuries in the intervention group for an incidence rate of 16.7%. Thus, in this study, the number of lower extremity overuse injuries was significantly lower infantry basic trainees with increased hamstring flexibility.     

Special relationship of gamma-aminobutyric acid to the ventromedial nucleus of the hypothalamus during embryonic development

The ventromedial nucleus of the hypothalamus (VMH) is a key nucleus for regulating homeostatic, neuroendocrine, and behavioral functions. We conducted immunocytochemical analyses by using antisera directed against gamma-aminobutyric acid (GABA), its synthetic enzyme glutamic acid decarboxylase (GAD67), GABA-A receptor subunits (alpha2, beta3, epsilon), estrogen receptor-alpha, and Neuropeptide Y (NPY) in the region of the VMH in embryonic mice to identify potential patterning elements for VMH formation. Cells and fibers containing GABA and GAD67 encircled the primordial VMH as early as embryonic day 13 (E13) when the cytoarchitecture of the VMH was not recognizable by Nissl stain. At E16-17 the cytoarchitecture of the VMH became recognizable by Nissl stain as GABAergic fibers invaded the nucleus, continued postnatally, and by adulthood the density of GABAergic fibers was greater inside than outside the VMH. GABA-A receptor subunit expression (beta3 by E13 and alpha2 by E15) within the primordial VMH suggested potential sensitivity to the surrounding GABA signal. Brain slices were used to test whether fibers from distal or proximal sites influenced VMH development. Coronal Vibratome slices were prepared and maintained in vitro for 0-3 days. Nissl stain analyses showed a uniform distribution of cells in the region of the VMH on the day of plating (E15). After 3 days in vitro, cellular aggregation suggesting VMH formation was seen. Nuclear formation in vitro suggests that key factors resided locally within the coronal plane of the slices. It is suggested that either GABA intrinsic to the region nearby the VMH directly influences the development and organization of the VMH, or along with other markers provides an early indicator of pattern determination that precedes the cellular organization of the VMH.     

Lessons from the eradication campaigns

Of seven global eradication programs this century, only two have relied primarily on vaccines for control measures - those against smallpox and poliomyelitis. Smallpox is history and polio could possibly achieve a similar status within the next decade. The hallmarks of these successful programs were surveillance and community outreach and involvement. However, a research agenda, so crucial to smallpox eradication, has largely been ignored or dismissed by polio program managers. This could prove to be a serious, even fatal error.