Ki67 LABELLING INDEX: AN INDEPENDENT PREDICTOR OF PROGRESSION IN PROSTATE CANCER TREATED BY RADICAL PROSTATECTOMY

The clinical course of prostate cancer is highly variable and cannot satisfactorily be predicted by histological criteria alone. Both tumour cell proliferation and neuroendocrine differentiation have been suggested as additional prognostic parameters, neuroendocrine differentiation being considered to enhance tumour cell proliferation. This study investigated the prognostic value of tumour cell proliferation [Ki67 labelling index (LI), MIB 1] and neuroendocrine differentiation and their relationship to each other. One hundred and thirty-seven paraffin-embedded radical prostatectomy specimens were examined. Neuroendocrine differentiation was found in 58 per cent of cases, but was not associated with pTN stage, Gleason score, Ki67 LI, or tumour progression. Ki67 LI was not significantly associated with pTN stage or with Gleason score. High grade ( P =0·0005), advanced local stage ( P =0·0004), positive lymph nodes ( P =0·02), and high Ki67 LI ( P =0·0203) were predictors of tumour progression if univariate analysis was performed, but Cox stepwise regression showed that only advanced local stage ( P =0·0025) and Ki67 LI ( P =0·0105) were independent predictors of tumour progression, the relative risk being 3·6 and 2·5, respectively. It is concluded that Ki67 is an important prognostic marker in prostate cancer with a potential for routine application.     

A new metric for quantifying performance impairment on the psychomotor vigilance test

We have developed a new psychomotor vigilance test (PVT) metric for quantifying the effects of sleep loss on performance impairment. The new metric quantifies performance impairment by estimating the probability density of response times (RTs) in a PVT session, and then considering deviations of the density relative to that of a baseline‐session density. Results from a controlled laboratory study involving 12 healthy adults subjected to 85 h of extended wakefulness, followed by 12 h of recovery sleep, revealed that the group performance variability based on the new metric remained relatively uniform throughout wakefulness. In contrast, the variability of PVT lapses, mean RT, median RT and (to a lesser extent) mean speed showed strong time‐of‐day effects, with the PVT lapse variability changing with time of day depending on the selected threshold. Our analysis suggests that the new metric captures more effectively the homeostatic and circadian process underlying sleep regulation than the other metrics, both directly in terms of larger effect sizes (4–61% larger) and indirectly through improved fits to the two‐process model (9–67% larger coefficient of determination). Although the trend of the mean speed results followed those of the new metric, we found that mean speed yields significantly smaller (～50%) intersubject performance variance than the other metrics. Based on these findings, and that the new metric considers performance changes based on the entire set of responses relative to a baseline, we conclude that it provides a number of potential advantages over the traditional PVT metrics.     

Brief Report: Transplantation of Allogeneic Canine Bone Marrow Stored at -80 C. in Dimethyl Sulfoxide

Prompt initial bone marrow engraftment was observed in 10 lethally irradiated dogs receiving infusions of 9.8 to 30.0 x 10⁹ allogeneic marrow cellsstored at -80 C. in dimethyl sulfoxide. The 3 recipients of bone marrow fromunrelated donors, mismatched by canine histocompatibility testing, subsequently rejected their grafts and died within 16 days with marrow hypoplasia.The 3 dogs with matched unrelated donors and the 4 with matched littermate donors all showed sustained marrow engraftment. Evidence of marrowrepopulation by allogeneic cells was obtained by cytogenetic studies in oneand by change to donor red cell type in 3 instances.

Submitted on December 16, 1968 Accepted on January 28, 1969     

Automatic Implantable Cardioverter Defibrillator/Permanent Pacemaker Interaction: Loss of Pacemaker Capture Following AICD Discharge

A 78-year-old man treated with amiodarone for recurrent ventricular tachycardia, had sequential placement of a bipolar VVI pacemaker and an automatic implantable cardioverter defibrillator (AICD). During defibrillation threshold testing, there was failure to capture of the pacer in the post-shock period. The time of failure to capture appeared energy-related: the greater the energy delivered, the longer the failure to capture. Careful attention will be necessary in constructing combined AICD/pacemaker units.     

LOW MOLECULAR WEIGHT IgM IN B CELL LYMPHOPROLIFERATIVE DISORDERS

Circulating low molecular weight (LMW) IgM was demonstrated in five of 38 patients with B cell lymphoproliferative disorders. These five patients all had malignant disease and could be subdivided into two groups. In the first group were three patients, each with an associated serum IgM paraprotein; two had Waldenstrom's macroglobulinemia. and one lymphocytic lymphoma. The two patients of the second group did not have IgM paraproteins; one had lymphocytic lymphoma and one chronic lymphocytic leukemia. Both these patients also had acquired C1 esterase inhibitor deficiency, a previously recognised association with circulating LMW IgM. None of the 16 patients with benign IgM macroglobulinemia had circulating LMW IgM. In those positive sera with LMW IgM this moiety contributed between 10.5% and 37.5% of the total IgM. There was no apparent association between LMW IgM and total IgM levels, kappallambda typing or the presence of Bence Jones proteinuria. but rheumatoid factor, immune complexes and cryoglobulins occurred in many of the sera which contained LMW IgM. Pokeweed mitogen stimulated peripheral blood mononuclear cells from two patients with circulating LMW IgM secreted considerable quantities of this moiety in vitrobut this did not occur in two patients with benign IgM macroglobulinemia. We conclude that LMW IgM is found in the malignant but riot the benign forms of B cell lymphoproliferative disorders and is frequently associated with other serological abnormalities. The basic abnormality causing defective IgM polymerisation in these disorders is obscure.     

The Relationship Between Sinoatrial Conduction Time and Sinus Cycle Length Revisited

In 1974 we reported an inverse relationship between sinoatrial conduction time (SACT) and sinus cycle length (SCL) during sinus arrhythmia utilizing the indirect atrial premature stimulation technique for estimating SACT, However, this behavior seemed anomalous try analogy with the AV node. Subsequent to 1974, methodological considerations about and limitations of the indirect techniques for estimating SACT became apparent, making us question our former impression. When the capability to directly record sinus node electrograms was developed and established in the 1980s, we had the means to reevaluate the SACT/SCL relationship. This report presents our findings in 40 patients: the SACT/SCL relationship is direct, not inverse. Moreover, we also show that during the phasic fluctuations of sinus arrhythmia, the P-P alterations are initiated more frequently by changes in sinoatrial conduction time than by changes in sinus cycle length.     

Protective ventilation to reduce inflammatory injury from one lung ventilation in a piglet model

Objectives: To test the hypothesis that protective ventilation strategy (PVS) as defined by the use of low stretch ventilation (tidal volume of 5 ml·kg^?1 and employing 5 cm of positive end expiratory pressure (PEEP) during one lung ventilation (OLV) in piglets would result in reduced injury compared to a control group of piglets who received the conventional ventilation (tidal volume of 10 ml·kg^?1 and no PEEP). Background: PVS has been found to be beneficial in adults to minimize injury from OLV. We designed the current study to test the beneficial effects of PVS in a piglet model of OLV. Methods: Ten piglets each were assigned to either ‘Control’ group (tidal volume of 10 ml·kg^?1 and no PEEP) or ‘PVS’ group (tidal volume of 5 ml·kg^?1 during the OLV phase and PEEP of 5 cm of H₂O throughout the study). Experiment consisted of 30 min of baseline ventilation, 3 h of OLV, and again 30 min of bilateral ventilation. Respiratory parameters and proinflammatory markers were measured as outcome. Results: There was no difference in PaO₂ between groups. PaCO₂ (P < 0.01) and ventilatory rate (P < 0.01) were higher at 1.5 h OLV and at the end point in the PVS group. Peak inflating pressure (PIP) and pulmonary resistance were higher (P < 0.05) in the control group at 1.5 h OLV. tumor necrosis factor‐alpha (P < 0.04) and IL‐8 were less (P < 0.001) in the plasma from the PVS group, while IL‐6 and IL‐8 were less (P < 0.04) in the lung tissue from ventilated lungs in the PVS group. Conclusions: Based on this model, PVS decreases inflammatory injury both systemically and in the lung tissue with no adverse effect on oxygenation, ventilation, or lung function.     

Modifying infant stress responses to major surgery: spinal vs extradural vs opioid analgesia

Twenty-six infants due to undergo major abdominal or thoracic surgery under general anaesthesia were randomized to receive additional analgesia with group A) spinal/epidural analgesia; B) epidural analgesia or C) opioid analgesia with fentanyl. We wished to determine if spinal analgesia followed by epidural analgesia might result in more complete control of cardiovascular or stress responses than the other two treatment groups. Heart rate and blood pressure were recorded at five min intervals throughout surgery. Blood samples were taken for measurement of catecholamines and whole blood sugar on induction, 45 min after skin incision and at the end of surgery. Heart rate rose significantly at the start of surgery in groups B and C but not group A. Systolic blood pressures were higher in group C compared to A and B. The rise in plasma glucose concentrations was significantly different between the groups in the order C>B>A (P<0·05). A similar trend was seen in the plasma adrenaline and noradrenaline concentrations but this failed to achieve significance due to the limited sample size.