Ilioinguinal block dissection for malignant melanoma

A retrospective analysis of 41 patients treated for metastatic inguinal lymph node malignant melanoma is presented: 16 underwent inguinal node excision and 25 ilioinguinal node excision. The two groups were well matched for age, sex and other characteristics. The mean time in hospital (inguinal 20 days, ilioinguinal 18 days) and the complication rates (inguinal, ten of 16 patients, ilioinguinal, 13 of 25) were similar in each group. The incidence of groin relapse, defined as the development of symptomatic melanoma in the region of the inguinal or iliac node basins following block dissection, was lower after ilioinguinal block dissection (inguinal, three patients; ilioinguinal, none). Histological examination demonstrated a high proportion of iliac node involvement (13 of 25 patients), even in those with a single mobile inguinal lymph node clinically and no clinical or computed tomographic evidence of iliac node involvement. This supports the value of ilioinguinal block dissection and suggests that the associated morbidity need not be greater than that associated with inguinal clearance alone.     

Structural destabilization of synaptosomal particles by lysis and sequential chemical treatments

Synaptosomes from rat brains were subjected to a sequence of treatments: osmotic lysis, buffered saline wash, nonionic detergent, EGTA and EDTA. After each treatment, particulate samples were fixed in 2% glutaraldehyde-1% formaldehyde and centrifuged to form pellets which were then processed for and examined by electron microscopy. Five morphological classes of synaptic particle were defined in terms of character and presence of synaptic vesicles, flocculent and stranded material, designated as intervesicular scaffolding (IVS), and presynaptic membrane. During osmotic lysis, the presynaptic compartment was altered by loss of most, but not all, small synaptic vesicles, by increase in proportion of large vesicles, and by disappearance of the presynaptic densities. The retention of vesicles was interpreted in terms of IVS struts interconnecting anchorage sites on synaptic vesicles and the presynaptic junctional membrane. Treatment of lysed synaptosomes with nonionic detergent or EGTA resulted in loss of vesicles and IVS from the junctional region in most particles. The apposition of pre-and postsynaptic junctional membranes along the synaptic cleft was disrupted more by EGTA than by detergent. The final result of the sequential treatments was a sediment containing a high proportion of synaptic particles, about half of which had lost their presynaptic junctional membranes.     

Extracellular adenosine 5'-triphosphate (ATP) in the endolymphatic compartment influences cochlear function

There is strong evidence for the presence of P2 purinoceptors on cochlear tissues, but the role of extracellular ATP in cochlear function is still unclear. Our previous studies have determined the presence of ATP in the cochlear fluids and indicated that the purinoceptors are substantially localized to the tissues lining the endolymphatic compartment. This implies that extracellular ATP may have an humoral role confined to the endolymphatic space. In order to study the influence of extracellular ATP in the endolymphatic space, a series of studies were undertaken in which ATP (10 microM to 10 mM) in artificial endolymph (EL) (test solution: 2-12.5 nl) was injected into the scala media and the effect on the cochlear microphonic (CM) and endocochlear potential (EP) evaluated. A double-barrelled pipette, with one barrel containing the test solution and the other artificial EL (control solution) was inserted into scala media of the third turn of the guinea-pig cochlea. A known volume (2-12.5 nl) of test or control solution was then pressure-injected into the space. ATP had a significant dose-dependent suppressive effect on both EP and CM with a threshold of approximately 2 x 10(-14) mol; the response was readily reversible, also in a dose-dependent fashion. Artificial EL of the same volume had no effect on EP and CM. The ATP effect on EP was blocked by the P2 purinoceptor antagonists suramin and reactive blue 2 (RB2). Neither adenosine (2 x 10(-13) to 2 x 10(-11) mol) nor suramin or RB2 on their own had any effect on EP and CM. This study provides the first evidence for an effect of extracellular ATP in the endolymphatic compartment on cochlear function which is mediated via P2 purinoceptors. This provides supporting evidence for an humoral role for extracellular ATP in the modulation of cochlear function.     

Temporal reduction in acute rejection after heart transplantation is not associated with a reduction in cell-mediated responses to donor-specific vascular endothelium

BACKGROUND: Over the first 6 months after clinical transplantation, the incidence of rejection falls despite typically substantial decreases in maintenance immunosuppression. Despite this, chronic vascular rejection, manifested by an accelerated form of coronary artery disease is usually evident by the first annual angiogram and continues to progress over subsequent years. METHODS: To investigate this phenomenon further, peripheral blood mononuclear cells were prepared from blood samples obtained from 42 cardiac allograft recipients at 1 week, 3 months, and 6 months after transplantation and co-cultured with endothelial cells isolated and cultured from the aortas of their specific cardiac allograft donors. Donor-specific alloreactivity was assessed by (1) peripheral blood mononuclear cell proliferation (3H-thymidine incorporation) and (2) up-regulation of endothelial cell major histocompatibility complex class I and class II antigens and ICAM-1 expression (flow cytometry) at all three time points. RESULTS: Over this 6-month period, rejection incidence fell from 0.68 rejections/patient to 0.12 rejection/patient. Cyclosporine dose was reduced from 5.6 +/- 0.3 mg/kg (mean +/- standard error of the mean) to 4.5 +/- 0.2 mg/kg, prednisone dose was reduced from 0.58 +/- 0.08 mg/kg to 0.17 +/- 0.02 mg/kg, and azathioprine remained constant at approximately 2 mg/kg over the 6-month period. Despite this reduction in rejection and immunosuppression, no measure of in vitro donor-specific cell-mediated response to endothelial cells decreased over the 6-month time period. Peripheral blood mononuclear cell proliferation in response to donor-specific endothelial cells was unchanged between 1 week (916 +/- 139 counts/min [cpm]) and 3 months (896 +/- 135 cpm) and increased at 6 months (1738 +/- 243 cpm, p < 0.01). The increase in endothelial cell major histocompatibility complex class II expression in response to recipient peripheral blood mononuclear cells likewise was unchanged between 1 week (42.5 +/- 7.8 mean channel shift [mcs]) and 3 months (34.7 +/- 6.6 mcs) and increased substantially at 6 months (95.4 +/- 17.2 mcs, p < 0.02). The magnitude of the increase in endothelial cell major histocompatibility complex class I antigen and ICAM-1 expression in response to co-culture with recipient peripheral blood mononuclear cells did not change over the 6-month period. CONCLUSIONS: These data suggest an important dichotomy between cell-mediated responses to allograft parenchyma versus those to allograft vasculature and may provide an explanation for progressive vascular disease despite the absence of acute rejection.