The ''think test'': a further technique to elicit hyperventilation.

Hyperventilation can undermine cardiovascular homeostasis by generating autonomic imbalance, sympathetic dominance, hypokalaemia, and intracellular alkalosis with calcium ion shifts. The role of hyperventilation in episodic disorders such as arrhythmia and coronary vasospasm can be difficult to identify if the patient does not present in an attack and so a provocation challenge is required. Today, the standard challenge is the forced hyperventilation provocation test (FHPT). A capnograph enables the resting end-tidal PCO2 to be compared with the level 3 min after the period of overbreathing. We report the use of a patient-specific challenge. After the FHPT, the subject is invited to close his eyes and think about the circumstances of an attack, feelings and sensations experienced (breathing is not mentioned) or topics that were seen to disturb the rhythm of breathing when the medical history was taken. A fall of end-tidal PCO2 of 10 mmHg or more lasting at least one minute was taken as a positive response. Out of 57 patients with cardiovascular symptoms suggesting a hypocapnic influence, resting hypocapnia (end-tidal PCO2 = 30 mmHg) was present in 3 (5%). Of the remaining 54, the FHPT was positive in 16 (30%) and the 'think test' in 33 (61%). This suggests that patient-specific stimulation has advantages over an unspecific challenge in testing for episodic hypocapnia.     

Persistent sciatic artery. Report of three cases and literature review

Persistence of the sciatic artery (SA) is a rare vascular anomaly, resulting from lack of regression of an embryonal artery to the lower extremity. Forty-nine cases have been published in the world literature since 1832. The persistent sciatic artery (PSA) is particularly prone to undergo aneurysm formation or atherosclerosis. It originates from the internal iliac artery, courses in close proximity to the sciatic nerve, and provides the main supply to the popliteal artery because a hypoplastic superficial femoral artery (SFA), contributing only collaterals to the knees, is usually associated with a PSA. This anomaly should be kept in mind in the clinical assessment of a pulsatile gluteal mass. It also presents a potential hazard during hip and renal transplant surgery.     

Cysteine Conjugate beta-Lyase-Dependent Metabolism of Compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene) in Human Subjects Anesthetized with Sevoflurane and in Rats Given Compound A

Background: Sevoflurane undergoes Baralyme- or soda lime-catalyzed degradation in the anesthesia circuit to yield compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene), which is nephrotoxic in rats and undergoes metabolism via the cysteine conjugate beta-lyase pathway in those animals. The objective of these experiments was to test the hypothesis that compound A undergoes beta-lyase-dependent metabolism in humans.

Methods: Human volunteers were anesthetized with sevoflurane (1.25 minimum alveolar concentration, 3%, 2 l/min, 8 h) and thereby exposed to compound A. Urine was collected at 24-h intervals for 72 h after anesthesia. Rats, which served as a positive control, were given compound A intraperitoneally, and urine was collected for 24 h afterward. Human and rat urine samples were analyzed by19 F nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry for the presence of compound A metabolites.

Results: Analysis of human and rat urine showed the presence of the compound A metabolites [S-[2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-N-acetyl-L-cysteine, (E)- and (Z)-S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-N-acetyl-L-cyst eine, 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid, 3,3,3-trifluorolactic acid, and inorganic fluoride. The presence of 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid and 3,3,3-trifluorolactic acid in human urine was confirmed by gas chromatography-mass spectrometry.     

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.      

Transformation of alveolar type 2 cells to type 1 cells following exposure to NO2.

This research was undertaken to study the fate of Type 2 cells after they have divided. To accomplish this, male rats were exposed to NO₂ to increase the number of dividing Type 2 cells. Dividing cells were labeled with ³H-TdR and studied with autoradiographic techniques in the electron microscope for up to 14 days after labeling. The results show that initially most of the ³H-TdR labeled cells were Type 2. However, by 2 days there was a decrease in frequency of labeled Type 2 cells and a large increase in labeled Type 1 cells. The new frequencies of labeled alveolar epithelial cells were stable from 2 through 14 days. This evidence supports the interpretation that Type 2 cells may transform into Type 1 cells. In addition, it was shown that under the conditions of this experiment: (1) the time for transformation was about 2 days, and (2) during this process an intermediate cell type was present.     

Increased rate of DNA recovery from United Kingdom epidemic Clostridium difficile PCR ribotype 1 strains stored cryogenically

We noted that some Clostridium difficile isolates are nonrecoverable after frozen storage and so used molecular typing analysis to characterize DNA from these strains. The recovery rate of C. difficile PCR ribotype 1 was statistically significantly greater than that of other strains. This observation has implications for C. difficile epidemiological studies.     

Cannabinoid agonist, CP 55,940, facilitates intake of palatable foods when injected into the hindbrain

Cannabinoids have been shown to influence food intake, and until recently, the neural pathways mediating these effects have remained obscure. It has been previously shown that intracerebroventricular injection of delta-9-tetrahydrocannabinol (Δ⁹-THC) causes increased consumption of palatable foods in rats, and we postulated the involvement of the hindbrain in this cannabinoid-induced food intake. Cannulated rats (both female and male groups) trained to consume sweetened condensed milk received either lateral or fourth ventricle injections of CP 55,940 and were presented with sweetened condensed milk 15 min after injection. Rats were injected over a range of doses between 100 pg and 10 μg per rat. Milk intake was recorded for a total of 3 h. Lateral ventricle injection of CP 55,940 increased milk intake at doses in the microgram range. However, CP 55,940 was effective in increasing food intake at nanogram doses when injected into the fourth ventricle. Finally, male rats appeared to be more sensitive to CP 55,940 than female rats inasmuch as milk consumption was increased at the 1 ng dose in male rats, whereas only the 10 ng dose was effective in females. These results indicate that CP 55,940 may act in the hindbrain to influence feeding behavior in rats.     

Ligament tissue engineering: an evolutionary materials science approach

The anterior cruciate ligament (ACL) is important for knee stabilization. Unfortunately, it is also the most commonly injured intra-articular ligament. Due to poor vascularization, the ACL has inferior healing capability and is usually replaced after significant damage has occurred. Currently available replacements have a host of limitations, this has prompted the search for tissue-engineered solutions for ACL repair. Presently investigated scaffolds range from twisted fiber architectures composed of silk fibers to complex three-dimensional braided structures composed of poly (l-lactic acid) fibers. The purpose of these tissue-engineered constructs is to apply approaches such as the use of porous scaffolds, use of cells, and the application of growth factors to promote ligament tissue regeneration while providing mechanical properties similar to natural ligament.