Myocardial Depressant Effects of Desflurane: Mechanical and Electrophysiologic Actions In Vitro

Background: The authors determined whether desflurane altered myocardial excitation-contraction coupling and electrophysiologic behavior in the same manner as isoflurane and sevoflurane.

Methods: The effects of desflurane on isometric force in guinea pig ventricular papillary muscles were studied in modified standard and in 26 mm K+ Tyrode solution with 0.1 [mu]m isoproterenol. Desflurane effects on sarcoplasmic reticulum Ca2+ release were also determined by examining its actions on rat papillary muscles, guinea pig papillary muscles in low-Na+ Tyrode solution, and rapid cooling contractures. Normal and slow action potentials were recorded using a conventional microelectrode technique. Ca2+ and K+ currents of guinea pig ventricular myocytes were examined.

Results: Desflurane (5.3% and 11.6%) decreased peak force to approximately 70% and 40% of the baseline, respectively, similar to the effects of equianesthetic isoflurane concentrations. With isoproterenol in 26 mm K+ Tyrode solution, desflurane markedly depressed late peaking force and modestly depressed early peak force. The rested state contractions of rat myocardium or guinea pig myocardium in low-Na+ Tyrode solution were modestly depressed, whereas rapid cooling contractures were virtually abolished after desflurane administration. Desflurane significantly prolonged the action potential duration. Desflurane reduced L-type Ca2+ current and the delayed outward K+ current but did not alter the inward rectifier K+ current.     

Kidney Transplantation in Patients with Antibodies against Donor HLA Class II

The immunologic risk associated with donor-specific antibodies (DSA) against Class II human leukocyte antigens (HLA) in kidney transplant (KTx) recipients is unclear. The aim of this study was to determine the outcome of KTx when DSA was detected only against HLA Class II. To isolate the impact of anti-Class II DSA, we retrospectively analyzed 12 KTx recipients who at baseline had a positive B-cell flow cytometric crossmatch (FXM) and a negative T-cell FXM. Using alloantibody specification analysis, 58.3% (7/12) had DSA against donor Class II and 41.7% had no demonstrable DSA. Biopsy-proven AMR occurred in 57% (4/7) in the Class II(+) group and 0% in the Class II(-) group (p > 0.05). Peritubular capillaries stained positive for C4d in 86% (6/7) of the Class II(+) patients and in 40% (2/5) of the Class II(-) patients (p > 0.05). One patient in the Class II(+) group lost their graft at 3 months to accelerated transplant glomerulopathy, while all other grafts were functioning 3-37 months posttransplant despite the persistence of anti-Class II DSA. We conclude that KTx recipients with clearly defined anti-Class II DSA are at risk for humoral rejection suggesting that desensitization and/or close posttransplant monitoring may be needed to prevent AMR.     

Comparison of the effects of three different combinations of general anesthetics on the electroretinogram of dogs

The objective of this study is to compare the effects of three different anesthetic combinations on the electroretinogram in the same animals under similar laboratory conditions. Thiopental–isoflurane (TI), medetomidine–ketamine (MK), and xylazine–ketamine (XK) were used on each of 12 healthy miniature schnauzer dogs (MS) with a period of at least 3 weeks in between subsequent anesthesia protocols, using the Dog Standard Protocol. The scotopic ERGs consisted of scotopic low stimulus strength (S) responses designated S1, S2, S3, S4, and S5, at 1, 5, 10, 15, and 20 min after dark adaptation, respectively, and scotopic standard stimulus strength (S-ST) responses. The photopic ERGs consisted of a photopic single flash (P) response and 31 Hz flicker (P-FL) responses. For S-ST (2.5 cd s/m²), the amplitude of the a-wave using TI was significantly lower than that using MK (adjusted P = 0.05) and XK (adjusted P = 0.03), and the implicit time of the a-wave was significantly shorter than that using MK (adjusted P = 0.04). For P (2.5 cd s/m²), the amplitude of the b-wave using XK was significantly higher than that using MK (adjusted P = 0.01). The implicit times of the b-wave using TI was significantly longer and shorter than that of MK for S1, S2 and P-FL and for S4 and S-ST, respectively, and than that of XK for S2 and P-FL and for S5 and S-ST, respectively. The results of the present study showed that TI affected both the amplitude and the implicit time of the a-wave for S-ST and the implicit time of the b-wave relatively more so than was the case when using XK or MK. Therefore, it appears that either XK or MK could be advantageous to use rather than TI for clinical studies.     

Notochordal cells stimulate migration of cartilage end plate chondrocytes of the intervertebral disc in in vitro cell migration assays

Background contextIt was recently demonstrated that the postnatal transition from a notochordal to a fibrocartilaginous nucleus pulposus (NP) is accomplished exogenously by chondrocytes migrating from hyaline cartilage end plates (CEs) into the ectopic notochordal NP region. Although our previous in vivo studies showed evidences for the migration of CE chondrocyte from hyaline CEs into the notochordal NP, it is unknown whether CE chondrocytes of the intervertebral disc (IVD) really have a motile property. In addition, the effect of notochordal cells on this property has not been elucidated.PurposeThe purpose of this in vitro study was to demonstrate whether CE chondrocytes of the IVD are capable of migration, and whether there is any biological link between notochordal cells and CE chondrocytes that may regulate the CE chondrocyte migration.Study design/settingIn vitro cell migration assays were performed using rat IVDs.MethodsNotochordal cells and chondrocytes were obtained from the NP and CE tissues, respectively, and were cultured separately. The different numbers of notochordal cells and the supernatant (conditioned medium) that contained soluble factors produced by notochordal cells were used to demonstrate their effects on the migration of CE chondrocytes. Bovine serum albumin (BSA) and lysophosphatidic acid (LPA) were used as negative and positive controls, respectively.ResultsCompared with BSA, LPA, notochordal cells (N=4×, 2×, 1×, and 0.5×10⁵), and its conditioned media (unconcentrated and fivefold concentrated) significantly increased migration of CE chondrocytes (p<.05 in all comparisons). Particularly, notochordal cells and its conditioned media increased migration in a number- and concentration-dependent manner, respectively.ConclusionsThis study demonstrates that CE chondrocytes of the IVD are capable of migration and that soluble factors produced by notochordal cells stimulate the migration. These results provide a plausible explanation to the question of why CE chondrocytes of the IVD migrate into the ectopic NP region during the natural transition from the notochordal to fibrocartilaginous NP.     

Traumatic cervical Brown-Sequard and Brown-Sequard-plus syndromes: the spectrum of presentations and outcomes.

Brown-Sequard syndrome (BSS) and Brown-Sequard-plus syndrome (BSPS) are characterised by asymmetrical paresis with hypalgesia more marked on the less paretic side. This study examined the clinical features of 38 patients (30 males and 8 females; mean age = 32 years) with traumatic cervical BSS or BSPS who underwent comprehensive inpatient rehabilitation. Twenty two injuries were caused by road traffic accidents, 8 by penetrating injuries, 5 by diving injuries, and 3 by other causes. After an average of 35 days in acute care and 79 days in rehabilitation, 37 patients had increased muscle strength, all 38 patients improved functional abilities, 29 patients walked independently, 34 had spontaneous bladder emptying, 36 were discharged home, and 14 were employed. Statistically significant increases (p less than 0.001) were made in modified Barthel index functional scores between admission and discharge. Patients with BSPS had a better prognosis than did those with 'pure' BSS. Patients with predominant upper limb weakness had more favourable outcomes than did those with predominant lower limb weakness. Few other potentially predictive demographic, injury, or neurological factors were associated with functional outcome. Patients with BSS or BSPS generally have a good prognosis for neurological and functional improvement.     

Chiropractic practice in Hong Kong: the need for amendments of health laws and provisions

Chiropractic practitioners with accredited qualifications should have the right to diagnose, the right to operate diagnostic imaging machines, and the right to the title doctor and Yee San. This paper reviews chiropractic practice in Hong Kong as well as laws and provisions of the health professions namely Chiropractors Registration Ordinance, Medical Registration Ordinance, Dentists Registration Ordinance, Radiation Ordinance, and the provisions of codes of practice of Medical Laboratory Technologists and Radiographers. The need for amendments of relevant sections of health laws and provisions, which concern chiropractic rights, chiropractic practice, and clinical research of mechanical neuromusculoskeletal disorders is discussed. Patient privileges relevant to chiropractic practice are proposed. The Chinese title Yee San or Yee and the English title Doctor are generic terms. Hence, legally “Yee San” and “Doctor” should not be coined by medical practitioners and vice versa. Diagnostic imaging and laboratory procedures are essential for differential diagnosis of neuromusculoskeletal disorders, which may indicate or contraindicate the application of manipulation, and hence are essential for chiropractic practice and clinical research. Proposed amendments of the listed sections of the ordinances and provisions are also outlined.     

Intraocular pressure and axial length in children

The intraocular pressure and the anteroposterior length of the eye are of great clinical importance for the diagnosis and management, before and after surgery, of congenital glaucoma. It is well-known that normal intraocular pressure in children is different from the normal levels in adults. We performed measurements of intraocular pressure and axial length in 141 children who had been admitted for eye problems other than glaucoma. The intraocular pressures were measured with the Perkins hand-held applanation tonometer at the beginning of general anesthesia. Simultaneously, A-scan ultra-sound measurements of the axial lengths of the eyes were made. In 10 children under the age of two years, the intraocular pressure was 11.85 +/- 1.35 mmHg. In 79 children from two to seven years, the intraocular pressure was 12.80 +/- 1.73 mmHg. In 52 children from seven to 15 years, the intraocular pressure was 13.31 +/- 1.79 mmHg. The axial lengths of the eyes in children under the age of two years, from two to seven years, and from seven to 15 years, were 21.31 +/- 0.97 mm, 22.04 +/- 0.92 mm, and 23.22 +/- 1.00 mm, respectively. These results were considered to be guidelines for measuring intraocular pressure and axial length in children suspected of having congenital glaucoma. The differences of intraocular pressures stated by other authors are due to early measurement of the intraocular pressure at the beginning of general anesthesia.     

Structural Characterization of Variant Forms of Arylsulfatase A that Associate with Alcoholism

Several electrophoretic forms of human platelet arylsulfatase A (ASA), including variant type III_a and normal type IV_a, have been identified by nondenaturing polyacrylamide gel electrophoresis. An alcoholic population that we have analyzed is enriched in variant type III_a compared with nonalcoholic psychiatric and normal controls. Individuals with the III_a enzyme possess greatly reduced levels of ASA activity. To understand further the structural basis for the differences and their potential biological consequences, the nature of the ASA variant expressed by fibroblasts from different individuals was explored. The electrophoretic patterns of fibroblast ASA from the III_a and IV_a individuals differ in degree of phosphorylation. Furthermore, fibroblast ASA from III_a individuals lacks an N -linked glycan found in ASA from IV_a individuals. In addition, differences in peptide and/or posttranslational modification unrelated to the N -linked carbohydrate or phosphorylation exist between the fibroblast ASA from III_a and IV_a individuals. The finding that both fibroblasts and platelets exhibit related electrophoretic isoform patterns characteristic of the donor's ASA type allows for the use of fibroblasts to study the impact of ethanol on the metabolism of cells possessing different ASA types.     

Somatic gene therapy for phenylketonuria and other hepatic deficiencies

Summary Gene therapy is the delivery of genetic material to specific cell types of an organism to alter its physiology or function. This technology is being explored as a means of treating diseases caused by deficiencies of hepatic gene products. The two diseases being used as models for hepatic gene therapy are classical phenylketonuria (PKU) and haemophilia B. Vectors derived from adenoviruses can be used to completely correct these diseases in animal models. The phenotypic correction generated in these studies is transient, and cannot be duplicated by vector readministration. The transient nature of transgene expression results from the destruction of the virally-transduced cells by a cellular immune response directed against the late viral gene products that are also expressed in the target cells. The inability to repeatedly administer virus is caused by a humoral immune response directed against viral proteins present at the time of infusion. If the host immune response is suppressed, transgene expression can persist for 6 months or more. These findings suggest that host immunomodulation in combination with further modification of the adenoviral vector to reduce or eliminate late viral gene expression may permit long-term expression of potentially therapeutic gene products in mammalian liver.     

Transforming Growth Factor-β1 Induces Apoptosis through Down-Regulation of c-mycGene and Overexpression of p27Protein in Cervical Carcinoma

Transforming growth factor-β1 (TGF-β1) is known to be a potent growth inhibitor for many cell types, including most epithelial cells. In skin keratinocytes, TGF-β1 has been shown to inhibit growth and to rapidly reduce c-mycexpression. However, the molecular mechanism of TGF-β1 action on cell growth of cervical carcinoma has not yet been elucidated. We thus assessed the effect of TGF-β1 on the growth of cervical carcinoma cell lines. Two cervical squamous carcinoma cell lines, CUMC-3 and CUMC-6, were incubated with varying concentrations of TGF-β1, and growth inhibition was evaluated with tetrazolium-based colorimetric assay. After culture in TGF-β1 for 24 h, inhibition of growth was detected in a dose-dependent manner at concentrations of 0.1–10 ng/ml in both cell lines. This effect of TGF-β1 on cultured carcinoma cells was associated with apoptotic process including oligonucleosomal ladder DNA and apoptotic body formations. Northern blot analysis revealed c-mycmRNA expression was suppressed by 10 ng/ml of TGF-β1 following 3 h of treatment in both cell lines. Western blot analysis showed that the level of p27^Kip1protein was increased after TGF-β1 treatment in both cell lines. These results suggest that the mechanisms by which TGF-β1 inhibits the growth of cervical carcinoma are complex and may include effects on down-regulation of c-mycgene, and overexpression of p27^Kip1protein.