Canine pancreas and kidney transplantation following total-lymphoid irradiation

The effect of total-lymphoid irradiation on survival of canine pancreas and kidney allografts was studied. TLI had a marked immunosuppressive effect as measured by in vitro immune responses and reduced circulating leukocytes. Despite the changes, median graft survival times for animals treated with 800 cGy (9 days) or 1800 cGy (9.5 days) were not significantly different from untreated control animals (7 days). The addition of low-dose antithymocyte globulin (10 mg/kg/day) on post-transplant days 0, 2, 4, 6, 8, and 10 had no measurable synergistic effect. Similarly, median segmental pancreas allograft survival times after 1700-2200 cGy of TLI treatment (16.5 days) were only marginally longer than those of untreated controls (9 days). The only animal to maintain a graft for greater than 200 days was matched to the donor in mixed lymphocyte culture (MLC). This animal was able to reject a third-party skin graft after 8 days while a graft from the original donor was still surviving after 21 days when the pancreas graft failed from a chronic-type rejection. These results indicate that TLI alone or in combination with ATG will not be predictably effective as a method of prolonging allograft survival. The role of matching major histocompatibility complex antigens in TLI treatment requires clarification.     

Manganese induced brain lesions inMacaca fascicularis as revealed by positron emission tomography and magnetic resonance imaging

A series of positron emission tomography scans was made on two monkeys during a 16-month period when they received manganese(IV)oxide by subcutaneous injection. The distribution of [¹¹C]-nomifensine uptake, indicating dopamine terminals, was followed in both monkey brains. The brain distributions of [¹¹C]-raclopride, demonstrating D₂ dopamine receptors, and [¹¹C]-l-dopa, as a marker of dopamine turnover, were followed in one monkey each. The monkeys developed signs of poisoning namely unsteady gait and hypoactivity. The [¹¹C]-nomifensine uptake in the striatum was reduced with time and reached a 60% reduction after 16 months exposure. This supports the suggestion that dopaminergic nerve endings degenerate during manganese intoxication. The [¹¹C]-l-dopa decarboxylation was not significantly altered indicating a sparing of [¹¹C]-l-dopa decarboxylation during manganese poisoning. A transient decrease of [¹¹C]-raclopride binding occurred but at the end of the study D₂-receptor binding had returned to starting values. The magnetic resonance imaging (MRI) revealed that the manganese accumulated in the globus pallidus, putamen and caudate nucleus. There were also suggestions of gliosis/edema in the posterior limb of the internal capsule. MRI might be useful to follow manganese intoxication in humans as long as the scan is made within a few months of exposure to manganese, i. e. before a reversal of the manganese accumulation.     

Pharyngeal swallowing in patients with paresis of the recurrent nerve

Pharyngolaryngeal function during swallowing was investigated cineradiographically in 22 patients with paresis of the recurrent nerve. Nineteen of these patients (86%) had defective closure of the laryngeal vestibule: 10 patients had defective apposition of the corniculate cartilages, (paresis of the oblique cricoarytenoid muscle), 9 patients had defective apposition of the arytenoid cartilages, (paresis of the interarytenoid muscle), 13 patients had defective movement of the epiglottis (paresis of, i.a. the thyrohyoid muscle), 1 patient had defective closure of the subepiglottic portion of the vestibule (paresis of the thyroepiglottic muscle), 2 patients had defective closure of the supraglottic portion of the vestibule (paresis of the superior ventricular segment of the thyroarytenoid muscle). Five patients with immobility of the epiglottis also had paresis of the pharyngeal constrictor musculature indicating paresis of the superior laryngeal nerve. Our investigation has shown that patients with paresis of the recurrent nerve who present with dysphagia with or without aspiration should be examined cineradiographically for pharyngolaryngeal function during swallowing.     

Determinants of survival in liver resection for colorectal secondaries

All 72 resections for colorectal liver secondaries during the period 1971-1984 were analysed retrospectively. Liver tumours were single in 35 (49 per cent), unilateral in 55 (76 per cent) and associated with extrahepatic disease in 12 (18 per cent) patients. Operative mortality was 5.6 per cent. With respect to the disease in the liver, the presence or absence of four or more metastases was the predominant prognostic determinant with a 5 year survival rate of 20 per cent in patients with less than four liver tumours, and no 3 year survivor among patients with four or more tumours. When the number of liver tumours was less than four, the prognosis in patients with unilateral disease was not significantly better than in patients with bilateral disease (P = 0.19). No other liver disease variable seemed to play any role in the prognosis. Extrahepatic disease was associated with a poor prognosis and no 5 year survivor. The length of the tumour-free resection margin was the only treatment variable that varied with the outcome: a resection margin of less than 10 mm was followed by a poor survival. Variables that did not influence survival included uni- or bilateral disease, liver tumour volume, tumour size, type of liver resection, Dukes' classification, differentiation of the primary tumour and synchronous or metachronous disease. It is concluded that resection for liver colorectal secondaries is indicated when there are less than four liver tumours, even if bilateral, no extrahepatic disease is present, and a resection margin of at least 10 mm can be obtained. It should not be performed unless all of these requirements are met.     

Longitudinal histopathologic assessment of rejection after bladder-drained canine pancreas allograft transplantation

In preparation for assessment of percutaneous biopsies in our clinical pancreas transplant program, a working knowledge of the histopathologic changes after transplantation was obtained in a longitudinal open biopsy study of 16 dogs receiving bladder-drained whole pancreas allografts. Edema, extravasation of polymorphs, and lymphocytes associated with focal parenchymal injury were early, invariable, and probably nonspecific findings. The initial feature of unmodified rejection was the appearance of capillary and small vein endothelial changes with mainly perivascular inflammatory cell infiltration. Acinar cell loss occurred early and was progressive, whereas islets and ducts were relatively preserved, indicating that acinar tissue may be more vulnerable to lytic necrosis when damaged. Functional rejection, determined by fasting urinary amylase levels, was at a stage of extensive and irreversible necrosis. Functioning grafts in immunosuppressed dogs had minor and transient endothelial changes with absence of class II antigen staining of parenchymal cells.     

Lipoproteins and metabolic control in hypertensive type II diabetics treated with clonidine

Twenty patients with type II diabetes mellitus and hypertension (WHO stages I and II) participated in a 3-month double-blind cross-over study to evaluate the effects of clonidine (75-300 micrograms daily) on blood pressure, glycemic control and plasma lipoproteins. Already after 1 month's treatment with clonidine the systolic and diastolic blood pressures had decreased, from 168/103 to 161/98 mmHg (p less than 0.01). Fasting blood glucose and HbA1c concentrations were unaffected by 3 months' treatment. Similarly, plasma lipid and lipoprotein concentrations remained unchanged throughout the study (i.e. mean high and low density lipoprotein cholesterol concentrations were 0.89 and 3.87 mmol/l on placebo vs. 0.90 and 3.98 mmol/l on clonidine). Adverse effects were mild and tolerable, and consisted mainly of dryness of the mouth. We conclude that clonidine lowers the blood pressure in patients with type II diabetes without any adverse effects on glycemic control or plasma lipoproteins.     

Muscle hypertrophy following 5‐week resistance training using a non‐gravity‐dependent exercise system

Aim: The efficacy of a mechanical, gravity‐independent resistance exercise (RE) system to induce strength gains and muscle hypertrophy was validated. Designed for space crew in orbit, this technique offers resistance during coupled concentric and eccentric actions by utilizing the inertia of a rotating flywheel(s), set in motion by the trainee. Methods: Ten middle‐aged (30–53 years) men and women performed four sets of seven maximal, unilateral (left limb) knee extensions two or three times weekly for 5 weeks. Knee extensor force and electromyographic (EMG) activity of the three superficial quadriceps muscles were measured before and after this intervention. In addition, with the use of magnetic resonance imaging (MRI), volume of individual knee extensor and ankle plantar flexor muscles was assessed. Results: Over the 12 training sessions, the average concentric (CON) and eccentric (ECC) force generated during exercise increased by 11% (P < 0.05). Likewise, maximal isometric strength (maximal voluntary contraction, MVC) at 90 and 120° knee angle increased by (P < 0.05) 11 and 12% respectively, after training. Neither individual quadriceps muscle showed a change (P > 0.05) in maximal integrated EMG (iEMG) activity. Quadriceps muscle volume increased by 6.1% (P < 0.05). Although the magnitude of response varied, all individual quadriceps muscles showed increased (P < 0.05) volume after training. As expected, ankle plantar flexor volume of the trained limb was unchanged (P > 0.05). Likewise, MVC, CON and ECC force, iEMG and knee extensor and plantar flexor muscle volume were unaltered (P > 0.05) in the right, non‐trained limb. Conclusion: The results of this study show that the present RE regimen produces marked muscle hypertrophy and important increases in maximal voluntary strength and appears equally effective as RE paradigms using gravity‐dependent weights, in this regard.