Local cerebral glucose utilization during intracerebral pH changes

The effect of ventriculocisternal perfusion with mock CSF with alkaline or acidic pH on the local CMRglu (LCMRglu) in the caudatoputamen was studied in artificially ventilated and relaxed rats. In control rats both lateral cerebral ventricles were perfused with mock CSF at pH 7.4. In the experimental series one cerebral ventricle was infused with normal mock CSF while the other was infused with mock CSF in which the pH was decreased or increased by changing [HCO-3]. LCMRglu was depressed in acidotic brain tissue while it was strongly increased in alkalotic brain tissue. The importance of these alterations in brain glucose metabolism for the homeostatic regulation of brain pH is discussed.     

Liver transplantation: patients' experiences

The Dutch orthotopic liver transplant programme was evaluated recently. This article focuses on the physical functioning, the pattern of activities, the social functioning and the level of wellbeing of 31 transplant patients. Data were generated by means of questionnaires and interviews. The majority of the patients look upon themselves as 'healthy'. Their physical potential has greatly improved. Three-quarters of the patient group think they are able to go back to work. However, from the interviews it appears that one third of the patient group suffered from more or less serious psychological problems following transplantation.     

In vitro modulation of cisplatin cytotoxicity by sparsomycin inhibition of protein synthesis

Inhibition of protein synthesis can alter cellular responsiveness to the classical anticancer drugs. The in vitro response of Chinese hamster ovary (CHO) cells to cisplatin with or without sparsomycin (Sm) was studied with the use of [3H]leucine and [methyl-3H]thymidine incorporation and clonogenic assay. Pretreatment of exponentially growing CHO cells with 1 microgram Sm/ml for 3 or 5 hours decreased [3H]leucine incorporation by 20% and resulted in significant resistance to cisplatin (P = .005). Sm in a concentration of 10 micrograms/ml reduced [3H]leucine and [methyl-3H]thymidine incorporation after 3 hours by 92 and 84%, respectively, and resulted in potentiation of the cisplatin cytotoxicity (P = .004). This effect was the same in the case of nonproliferating cells (P = .005), while protection due to Sm (1 microgram/ml) was seen only during cell proliferation. Simultaneous incubation and postincubation with Sm proved to have much less or no potentiating effect on cisplatin. The mechanisms of both protection and potentiation are still not clear, but our data indicate that Sm is a promising drug for further studies on the modulation of the cancer cell response to classical anticancer drugs.     

Recombinant human interferon alpha increases oestrogen receptor expression in human breast cancer cells (ZR-75-1) and sensitizes them to the anti-proliferative effects of tamoxifen

Exposure of ZR-75-1 human breast cancer cells for 48 h to human recombinant interferon alpha (IFN alpha) resulted in increased expression of oestrogen receptors as measured in a whole cell binding assay. This effect was inversely proportional to dose being significant following treatment with 10-100 IU IFN ml-1 and was only observed at a low initial cell plating density. The extent of the increase in oestrogen receptor levels ranged from 1.2- to 7.2-fold following treatment with 10 IU IFN ml-1. No increase in progesterone receptor expression was observed under the same experimental conditions. Concentrations of IFN which increased oestrogen receptor levels had no effect on cell proliferation. IFN (500 IU ml-1) inhibited cell proliferation and the combination of this treatment with tamoxifen (2 microM) had a greater anti-proliferative effect than either drug alone although there was no evidence of synergism. However, a 5-day pretreatment of cells with IFN (10 IU ml-1) markedly sensitised them to the growth-inhibiting effect of a subsequent 6-day exposure to tamoxifen.     

Comparison of physiological responses to maximal arm exercise among able-bodied, paraplegics and quadriplegics

A comparison of pulmonary, cardiovascular and metabolic responses was made in 32 subjects consisting of 11 able-bodied, 8 paraplegics (T4-L3 lesions) and 13 quadriplegics (C5-C8 lesions) during maximal arm cranking exercise. A progressive continuous arm cranking test, modified for each group, was employed to elicit maximal responses with pulmonary and metabolic determinations made with open circuit spirometry and selected cardiovascular measurements made by impedance cardiography. Additionally, non-exercise static and dynamic lung function assessments were made. Quadriplegics had significantly lower (p less than 0.05) tidal volumes, vital capacities, forced expiratory volumes at 1 seconds, and maximal breathing capacities than the other two groups. The mean peak VO2 during maximal arm cranking was 28.2, 25.3 and 12.0 ml/kg.min for the able-bodied (AB), paraplegics (PP) and quadriplegics (QP), respectively. Furthermore, reduced cardiovascular function was observed in the QP as evident in the low peak HR (109 b/min), peak SV (52 ml/b) and peak Q (5.7 l/min). Values for the QP were 64% and 64% peak HR, 89% and 50% peak SV and 54% and 33% peak Q of values observed for the PP and AB groups, respectively. The peak SV and Q values were significantly lower (P less than 0.05) for the PP group when compared with the AB group. Although not statistically significant the estimated a-v O2 difference was higher for both spinal cord injured groups (14.0 and 14.6 ml O2/100 ml, PP and QP respectively). The impaired work capacity and reduced oxygen transport and utilisation of the QP group can be attributed to impaired sympathetic cardiac stimulation and a smaller available active muscle mass.     

Familial amyloidotic polyneuropathy: long-term follow-up of abdominal fat tissue aspirate in patients with and without liver transplantation.

To estimate the evolution of amyloid in tissue, we studied abdominal fat aspirates of cases with familial amyloidotic polyneuropathy (FAP) longitudinally at regular intervals between 1994 and 2006. In 22 cases (13 carriers and nine patients) not yet transplanted median follow-up was 3.3 years (range 0.4-11.3). We found a significant increase in the amyloid grade of fat tissue from 2+ to 4+ and from 0 to 4+ in two of three subjects with follow-ups of >7 years, after 7 and 11 years, respectively. All other subjects remained negative or did not show a significant change. In 11 liver transplant patients, follow-up with fat aspirate was available with a median duration of 3.1 years (range 1.0-10.1). A comparison was made with cardiac amyloid as judged by the cardiac septum diameter and the serum NT-ProBNP (N-terminal pro-B-type natriuretic peptide) level. No stable increase of amyloid in fat was seen in any patient. A stable decrease of amyloid grade was seen in one patient 5 years after transplantation. In contrast, the cardiac septum diameter increased >or=4 mm in six of the 11 transplant patients. Our study shows the diagnostic utility of a regularly repeated fat aspirate in carriers at risk for the development of ATTR amyloidosis. Evolution of amyloid deposition in fat tissue is very gradual. After liver transplantation, amyloid deposition in fat tissue seems to stabilize and may even decrease in the long term, whereas amyloid deposition in cardiac tissue appears to be progressive.     

The Manner Born: Birth Rites in Cross‐Cultural Perspective

Edited by Lauren Dundes. Walnut Creek (CA): Altamira Press, 2003. 239 pages. $27.95, paperback, $75.00, hardback.