Dose response relationships for radiation induced chromosome aberrations in human lymphocytes in vivo and in vitro

Chromosome aberrations have been analysed in cultured lymphocytes from a patient undergoing whole-body treatment with split doses of gamma-rays up to a cumulative dose of 1.4 Gy. The dependence on dose of the yield of dicentrics was best fitted to the linear-quadratic relationship with a linear component predominating in the low dose range (below 0.56 Gy). These observations were compared with the data obtained when blood samples were exposed in vitro to low acute doses of gamma-rays (from 0.05 up to 2.0 Gy). The frequencies of induced chromosome aberrations were similar in both cases and little deviation was found between the dose response curves (a/b ratio equal to 0.56 and 0.69 Gy, respectively in vivo and in vitro). These results confirm that in vitro calibration curves can be utilized confidently for the biological estimate of an in vivo absorbed dose.     

Uncemented two-component femoral prosthesis for the hip joint. A 50-month follow-up study

The Monk Duopleet femoral interlocking uncemented two-component endoprosthesis consists of a polyethylene cup covered by a metal cap and an Austin-Moore type stem. Seventy-two patients (average age, 71 years) were treated by this arthroplasty: 27 for subcapital femoral neck fracture, 36 for osteoarthritis, and nine as an exchange operation. Three patients died following operation. After a mean follow-up time of 50 months, 47 patients were reexamined clinically and radiographically. Because of loosening, four patients had the prosthesis removed. Twenty-six patients were classified as excellent, 12 as good, six as fair, and three as poor. There were no cases of acetabular intrusion. The Monk Duopleet prosthesis may solve the problem of the loosening that had been associated with femoral component alone. The long-term results are promising and appear to be better than the results of the standard Moore prosthesis. The Monk Duopleet prosthesis is an alternative to other two-component endoprostheses for the treatment of subcapital hip fractures and in the group of patients suffering from osteoarthritis, where an arthroplasty with a cemented prosthesis may be considered hazardous because of age or general disease.     

Endogenous dopaminergic asymmetry affects development of seizures kindled in the rat amygdala

Cerebral dominance in 56 rats was determined by observing the direction of their turning behavior in response to injection of d-amphetamine (1.5 mg/kg, i.p.). Rats subsequently subjected to kindling of the amygdala developed full epileptic seizures after significantly fewer kindling sessions if the kindling electrodes were in the amygdala of the nondominant, rather than the dominant hemisphere. Kindling rate also showed a significant negative correlation with the total amount of turning after amphetamine. Rats kindled through electrodes in the ventral mesencephalon generally failed to develop full convulsive seizures, and did not show interhemispheric differences in the rate at which they developed preictal behaviors. As the dominant hemisphere of the rat, identified by rotational preference, contains a higher concentration of dopamine, we conclude that even small differences in dopaminergic activity, within the normal physiologic range, can affect the relative susceptibility of the two hemispheres to the development of kindled epilepsy.     

Total lymphoid irradiation in chronic polyarthritis--a new therapeutic concept

Eleven patients with refractory rheumatoid arthritis were submitted to a total lymphoid irradiation up to a dose of 20 Gy. A constant improvement of clinical symptoms was observed in four out of the eleven patients already during the treatment and in the other patients not later than two months after. The frequency of attacks decreased and the number of joints involved in the attack was reduced. Morning rigidity and joint swellings decreased. One patient developed joint empyemas 4 and 26 months after the treatment. Four patients died in the meantime. In two patients the cause of death were renal insufficiency and a postoperative cardiogenic shock associated with generalized amyloidosis. The third patient died because of a toxically induced left cardiac decompensation with sepsis that could not be controlled by antibiotic drugs and multiple joint empyemas. The fourth patient developed an abscess after surgical treatment of a Kaposi syndrome. She died three months later from acute left cardiac decompensation. The therapy induced a lymphocytopenia with decrease of T helper lymphocytes and unchanged number of T suppressor lymphocytes. The constant therapy results of total lymphoid irradiation in primary chronic polyarthritis is probably due to this modification in the immune regulation.     

Adrenergic and dopaminergic control of the canine paw microcirculation

Basal isolated canine paw blood flow was equally distributed between arteriovenous anastomosis (AVA) and capillary circulations. Norepinephrine decreased AVA flow by 92% and capillary flow by 41%. Dopamine significantly reduced AVA flow by 94% compared to baseline with a 37% reduction in capillary flow. However, with alpha-adrenergic blockade dopamine decreased AVA flow 66% while capillary flow increased 42%. Isoproterenol increased capillary flow almost twofold and appeared to decrease AVA flow, although the latter was statistically insignificant. Differential effects of adrenergic and dopaminergic agonists on canine paw AVA and capillary blood flow suggest the existence of independent regulation of these components of the microcirculation.     

Mitogen responsiveness of lymphocytes from the BB/W rat

The response of BB diabetes-prone (DP) and W-line non-diabetes-prone rats to the T-cell mitogen concanavalin A (ConA) was measured. The W line was a good responder to ConA, whereas the DP was relatively unresponsive. This unresponsiveness could not be reversed with exogenous interleukin 2 (IL-2). The response of DP rats was enhanced by removing adherent cells. To directly test the response of BB T-cells, they were isolated by flow sorting. These experiments demonstrated that BB T-cells could mount a normal ConA response. The normal function of isolated BB T-cells suggested that they were under suppression. Suppressor activity could not be found in the OX8+ population but was found in the DP-adherent cell population. Adherent cells from the W line were not suppressive at the concentrations used. These results showed that the decreased mitogen responsiveness of BB T-cells was not due to an intrinsic T-cell abnormality but was due, in part, to suppression by adherent cells.     

Effect of warfarin on formation and growth of pre-neoplastic lesions in chemically induced colorectal cancer in the rat

Anticoagulant drugs are known to have an effect on tumour growth. However, the mechanisms by which they act are poorly understood, and have therefore been investigated in this study. Wistar rats were given eight weekly subcutaneous injections of azoxymethane, at a dose of 10 mg kg-1 week-1. Following this they were randomized into two groups: a control group, which received no further treatment, and a warfarin treated group, which received warfarin at 'non-therapeutic' doses in their drinking water, for a further 8 weeks. Pairs of rats from each group were killed at 5-weekly intervals from 10 to 35 weeks after the first azoxymethane injection. At 40 weeks all remaining rats were killed. Samples of colonic mucosa from the descending colon and rectum were taken for scanning electron microscopy. The number of microadenomas per low power field was determined in both groups at each time interval. Tumour incidence and distribution were noted in animals killed at 40 weeks. The median number of microadenomas was significantly lower in warfarin treated animals than in controls at all time intervals. Tumour number was also significantly decreased by warfarin treatment (27 in azoxymethane treated animals, 10 in animals receiving azoxymethane and warfarin, P less than 0.05). The distribution of tumours along the colon was similar to that seen previously, following 12 weeks of azoxymethane. These effects occurred despite the non-concurrent administration of azoxymethane and warfarin.