Delayed Nociceptive Response Following Cold-Water Swim in the Formalin Test: Possible Mechanisms of Action

Exposure of animals to aversive events produces stress-induced analgesia. A common method of producing stress in animals is the cold-water swim (CWS). The present series of experiments examines the effect of CWS on tonic pain, as measured by the formalin test, and explores possible mechanisms of action. Experiment 1 demonstrates that a 3.5-min swim in 2°C water produces a delayed nociceptive response (DNR), characterized by a prolonged period of no formalin responding which then begins and continues during the time when control animals, which have not received the CWS, are finished responding. The delayed response begins at 50–60 min postformalin injection, peaks at 80 min, and is still present at 120 min. Experiment 2 indicates that paw temperature effects are not responsible for the DNR, although core body temperature effects are a possible mechanism. However, systematic delays in the formalin injection following the CWS (Experiment 3) drastically altered the DNR even though core body temperature remained unchanged, suggesting that a decrease of core body temperature is insufficient to account for the DNR. Experiment 4 demonstrates that the NMDA antagonist MK-801 administered prior to the CWS dramatically reduces the DNR. The present experiment is the first study that reports a delay as long as 60 min in pain responding. It is concluded that the delayed response to formalin injection is the result of complex interactions involving peripheral mechanisms and central neuronal plasticity in which activity initiated by a noxious input persists after the cessation of the input as a consequence of a stressful event such as the cold-water swim.     

Percutaneous nephrolithotomy directlythrough an angiomyolipoma

We present a patient with tuberous sclerosis and bilateral angiomyolipomaswith a right partial staghorn calculi in which the calculi was managed with a percutaneous nephrolithotomy. Despite the inherent risk of hemorrhage with a percutaneous approach compounded by the fact that this was done directly through a tumor, we were able to render the patient stone free with no intraoperative bleeding, complications, or the need for postoperative blood transfusion. To our knowledge, this is the first reported case of percutaneous nephrolithotomy directly through a renal angiomyolipoma.     

Coma arousal procedure: A therapeutic intervention in the treatment of head injury

This study reports on the efficacy of a 'coma arousal procedure'. This procedure involved a programme of vigorous sensory stimulation administered to comatose patients by relatives using Comakits. An experimental group of 12 severely head-injured patients received the coma arousal procedure while a matched control group did not. Total duration of coma and weekly Glasgow Coma Scale Scores were recorded for the two groups. Results indicate that the total duration of coma was significantly shorter and that coma lightened more rapidly for the experimental group.     

Apoptosis in perinatal hypoxic-ischaemic cerebral damage

Perinatal hypoxia-ischaemia induces a biphasic cerebral injury: the depletion in high energy phosphates during the insult returns to normal soon after resuscitation. However, some 8–15 h later a second phase of impaired energy metabolism begins, which is related to the severity of later neurodevelopmental impairment. Delayed injury differs from acute hypoxia-ischaemia because intracellular acidosis does not occur. Apoptosis may be a mechanism of delayed cellular injury. Apoptotic cells and typical DNA fragmentation have been found after perinatal hypoxia-ischaemia. In newborn piglets, fraction of apoptotic cells was directly related to the degree of high energy phosphate depletion during hypoxia-ischaemia. Apoptosis may be interrupted: in piglets, brain cooling for 12 h following resuscitation reduced the fraction of apoptotic but not necrotic cells. These results have implications for both the understanding of cerebral injury and the use of hypothermia as a neural rescue strategy in the developing brain.     

Hydrogen peroxide-induced endothelial retraction is accompanied by a loss of the normal spatial organization of endothelial cell adhesion molecules.

Treatment of confluent monolayers of human umbilical vein endothelial cells with sublethal concentrations of hydrogen peroxide (H2O2) produces reversible cell retraction that opens gaps between adjacent cells. Despite the retraction, adjacent cells remain in contact through a network of dendrite-like processes. Retraction depends on cellular metabolism but not new protein synthesis or protein kinase C. Shape changes induced by H2O2 are accompanied by partial redistribution of actin filaments from the cell periphery in resting endothelial cells to a tangled network of centrally located filaments in H2O2-treated endothelial cells. This change in actin organization is associated with a loss of the normal distribution pattern of surface protein expression. Specifically, beta 1 and beta 3 integrins partly escape from focal adhesion plaques and migrate to the lateral and apical surface of the cell; PECAM-1 redistributes from the lateral borders to the basal surface; and ICAM-1 and ICAM-2 spread from apical caps to the basal surface and to the dendrite-like processes. The likely consequence of endothelial retraction accompanied by abnormal membrane protein distribution is a loss of normal endothelial cell functions. These changes are best considered manifestations of H2O2-induced sublethal injury that may cause endothelial dysfunction.     

Alternatives in the surgical management of in situ breast cancer. A meta-analysis of outcome

The surgical management of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS) remains controversial. For in situ breast cancer local excision (LE), local excision and radiation therapy (LERT) and mastectomy (MAST) have all been advocated. A search of the English literature found 13 reports concerning the surgical management of LCIS and 12 reports concerning the management of DCIS. The data were combined in a meta-analysis of outcome. As expected, recurrence rates following LE with both LCIS 8.4%) and DCIS (17%) are high. However,the overall mortality following mastectomy for recurrence, LCIS (2.8%) and DCIS (2.3%) does not differ statistically from those treated initially with mastectomy for LCIS (0.9%) and DCIS (1.7%). We conclude from these data that local recurrence after breast conserving procedures for in situ breast cancer does not carry an ominous prognosis. This knowledge should aid in planning individual therapy.     

Do viscous polysaccharides slow absorption by inhibiting diffusion or convection?

Viscous polysaccharides such as guar gum delay absorption probably by impairing the access of luminal contents to the absorptive epithelium. Measurements of the electrical resistivity of saline solutions were carried out to determine if guar gum (0.5, 0.75 and 1 per cent w/v), in concentrations which impaired absorption in vitro, delayed diffusion of solutes or inhibited convection of luminal contents. Our results indicated that guar had no effect on the mobility of ions in a completely unstirred solution but delayed the time taken for saline solutions of different resistivity to achieve complete mixing, when they were brought into contact inside a vessel, which was rotated at a constant speed. The time taken to achieve complete mixing was directly related to the viscosity of the guar solutions. The effect of intestinal contraction on the absorption of glucose was simulated in an in vitro model, consisting of a length of dialysis tubing, alternately contracted at each end. Movement of glucose out of the dialysis tubing was increased by increasing the rate of contraction. The incorporation of guar gum into the solution prevented the rise in glucose uptake produced by increasing the rate of contraction. These effects suggest that guar probably reduces absorption by resisting the convective effects of intestinal contractions.     

Evolution of white matter lesions in neurofibromatosis type 1: MR findings.

To characterize further the evolution of white matter lesions in neurofibromatosis type 1, we reviewed 68 MR images in 43 patients (age, 1-31 years), including 25 follow-up studies (mean interval, 27 months). Lesion number, location, morphology, signal characteristics, and contrast enhancement were assessed. Lesion characteristics and changes thereof were correlated with the patients' ages. Thirty-four patients (79%) had white matter lesions. These lesions were hyperintense on T2-weighted images, were isointense on T1-weighted images, and showed no mass effect or contrast enhancement in 31 patients; in three patients, T1-prolongation was observed (one with significant mass effect). None of the lesions evolved into a glioma. The most common locations were the cerebellum (49%), brainstem (22%), and internal capsule (19%). Nineteen patients had white matter lesions and follow-up studies. Lesions decreased in size or number in seven patients (average age, 13 years), showed no change in three (average age, 12 years), increased in size or number in four (average age, 5 years), and showed a mixed pattern (increased/decreased size/number) in four (average age, 7 years). White matter lesions in neurofibromatosis type 1 frequently increase in size or number early in childhood; this did not indicate neoplasia in our study. The lesions tend to resolve with increasing age. Lesion progression in a child more than 10 years old warrants close follow-up to rule out a neoplasm.