Distinct Membrane Effects of Spinal Nerve Ligation on Injured and Adjacent Dorsal Root Ganglion Neurons in Rats

Background: Painful peripheral nerve injury results in disordered sensory neuron function that contributes to the pathogenesis of neuropathic pain. However, the relative roles of neurons with transected axons versus intact adjacent neurons have not been resolved. An essential first step is identification of electrophysiologic changes in these two neuronal populations after partial nerve damage.

Methods: Twenty days after spinal nerve ligation (SNL), intracellular recordings were obtained from axotomized fifth lumbar (L5) dorsal root ganglion neurons and adjacent, intact L4 neurons, as well as from control neurons and others subjected to sham-SNL surgery.

Results: Pronounced electrophysiologic changes were seen only in L5 neurons after SNL. Both A[alpha]/[beta] and A[delta] neuron types showed increased action potential duration, decreased afterhyperpolarization amplitude and duration, and decreased current threshold for action potential initiation. A[alpha]/[beta] neurons showed resting membrane potential depolarization, and increased repetitive firing during sustained depolarization developed in A[delta] neurons. The afterhyperpolarization duration in neurons with C fibers shortened after axotomy. In contrast to the axotomized L5 neurons, neighboring L4 neurons showed no changes in action potential duration, afterhyperpolarization dimensions, or excitability after SNL. Depolarization rate (dV/dt) increased after SNL in L4 A[alpha]/[beta] and A[delta] neurons but decreased in L5 neurons. Time-dependent rectification during hyperpolarizing current injection (sag) was greater after SNL in A[alpha]/[beta] L4 neurons compared with L5. Sham-SNL surgery produced only a decreased input resistance in A[alpha]/[beta] neurons and a decreased conduction velocity in medium-sized cells. In the L5 ganglion after axotomy, a novel set of neurons, consisting of 24% of the myelinated population, exhibited long action potential durations despite myelinated neuron conduction velocities, particularly depolarized resting membrane potential, low depolarization rate, and absence of sag.     

Femoral anteversion related to side differences in hip rotation: Passive rotation in 1, 140 children aged 8-9 years

We assessed whether the range of passive hip motion is reliable for predicting abnormal femoral ante-version. We measured the passive medial and lateral rotation in extension in both hips of 1, 140 children between 8 and 9 years of age. The children were divided into 3 groups: group 1: difference between lateral and medial rotation less than 10° group 2: medial rotation more than 10° greater than the lateral; group 3: lateral rotation more than 10° greater than the medial. Group 1 comprised 90% of the children, whereas 8% belonged to group 2 and 2% to group 3.

The angle of femoral neck anteversion was measured in 57 children from the first group, in 67 from the second and in 24 children from the third group, using biplane radiography. The mean anteversion angles in the 3 groups were 24°, 36° and 14°, respectively. To predict an abnormally high anteversion angle (above mean +2SD), the difference between medial and lateral rotation must be 45° or more, whereas an abnormally low anteversion angle (lower than mean -2SD) could be predicted when the lateral rotation was at least 50° higher than the medial rotation.     

Systemic fungal infections in immunocompromised patients

Opportunistic fungal infections are becoming more frequent complications during cancer therapy, after organ transplantation and in AIDS infections, especially after better control of bacterial infections in immunocompromised patients. Periods of prolonged neutropenia with neutrophil count less than 0.5 x 10(9)/L longer than 7 days, are the most important risk factors for the development of systemic fungal infections. Especially susceptible are the patients during treatment of acute leukemia, or after bone marrow transplantation. The most frequent causing agents of systemic fungal infections are Candida and Aspergillus species, than Cryptococcus neoformans and Mucor. Some other unusual species such Fusarium, Trichosporon, non-albicans Candida species of Candida are becoming more frequent, and is frequently resistant to conventional therapy. The difficulties in early and precise diagnosis of fungal infections, and the lack of adequate and efficient drugs are responsible for the high mortality of immunocompromised patients, even in potentially curable diseases. The recognition of risk factors, introduction of prophylactic measures, application of empirical antifungal therapy, are the procedures for the reduction of morbidity and mortality of invasive fungal infections. Fluconazole administration in prevention of systemic fungal infections, has become the standard approach, especially after bone marrow transplantation, while the oral itraconazole solution, has even more extended activity. Fluconazole appears successful also in the treatment of systemic Candidiasis. Conventional amphotericin-B is still the "gold standard" in the treatment of fungal infections. The new lipid formulations of amphotericin-B, intravenous itraconazole, has an identical efficacy, but are less toxic than conventional amphotericin-B. Several new promising agents are in the stage of clinical investigation like voriconazole, caspofungin, mycafungin and some other.     

Biochemical changes in the sublingual and submandibular glands after interruption of chorda tympani

The left chorda tympani nerve was interrupted through meatus acusticus externus in ten dogs. In total, 40 dog salivary glands (20 submandibular and 20 sublingual) innervated via chorda tympani were examined. Twenty glands (10 submandibular and 10 sublingual) on the left side were deprived of parasympathetic innervation by chordectomy, whereas contraleteral glands, on the right side, served as controls. Biochemical analysis showed that the interruption of chorda tympani did not cause any significant changes in the concentrations of eight enzymes investigated, i.e. lactate dehydrogenase, alkaline phosphatase, acid phosphatase, amylase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase and creatine kinase. There were no significant changes in the concentrations of most important extracellular ions (sodium, potassium, chloride and phosphorus) in the right glands, but the loss of parasympathetic innervation in the left glands was found to cause a statistically significant decrease in the concentration of potassium as intracellular cation and of phosphorus as extracellular anion.     

Systemic and local expression of perforin in lymphocyte subsets in acute and chronic rheumatoid arthritis

OBJECTIVE: To investigate the role of the cytolytic action mediated by perforin in the course of rheumatoid arthritis (RA), we studied the immunophenotypic characteristics of lymphocytes containing perforin in peripheral blood (systemic level), in synovial fluid (SF), and in the synovial membrane (local level) in patients during the acute or chronic phase of RA. Cells from patients with osteoarthritis were used as controls. METHODS: Flow cytometry was used for simultaneous detection of intracellular (perforin) and cell surface antigens. Mean fluorescence intensity (MFI) was a measure of the mean perforin content per cell. Immunocytochemical staining was used to visualize perforin in the cytoplasmic compartment of cells. RESULTS: In acute RA highly significant changes in perforin expression were found in all compartments (peripheral blood, SF, and synovial membrane): (1) increase of percentage of total perforin positive cells; (2) increase of both subsets of cytolytic cells, T (CD8+P+) and NK (CD56+P+) cells; (3) increase in the frequency of perforin positive cells in CD8+ and CD56+ cell populations; and (4) the highest content of perforin/cell (MFI values) in all compartments, except in the synovial membrane. CONCLUSION: Perforin positive cells may participate in the acute phase of RA by maintaining and perpetuating inflammation and contributing to tissue destruction.