Quality down under: if we knew then what we know now

Australian health care's approach to performance improvement increasingly includes the use of total quality management (TQM) and its component principles and methods. Implementation experiences have confirmed TQM's relevance in the Australian health care environment, senior management's pivotal role, and the range of factors required for success. Ways of influencing executive behavioral change and streamlining implementation are discussed.     

N-CAM promotes recovery in injured nerves

The neural cell adhesion molecule, N-CAM, makes critical contributions to the development of the nervous system. It mediates the stability of homophilic adhesion in embryonic neurons and participates in morphologic differentiation. The goal of these studies was to determine N-CAM contributions to nerve regeneration and recovery of function in two species with an excised segment of sciatic nerve. N-CAM was isolated from embryonic brains, affinity purified and admixed in collagen gel for administration. Recovery was compared 30 days after surgery for two types of N-CAM delivery: entubulization versus direct application. For control nerves, tubes contained gel only. In preliminary chicken studies, latency of nerve responses was measured to demonstrate N-CAM's ability to improve upon spontaneous recovery. In subsequent studies of rodent nerves, the direct application of N-CAM significantly improved recovery in evoked nerve response amplitude, number of regenerated axons and behavioral activity. Results demonstrate N-CAM's ability to augment nerve regeneration and suggest a potential for therapeutic use.     

Isovelocity investigation of the lengthening behaviour of the erector spinae muscles

The purpose of this study was to investigate the force-velocity (F/) relationship for the erector spinae muscles in submaximal activation movements, with particular attention to their response during lengthening movements and at lower shortening contraction velocities. Dynamic models that predict lower back muscle forces require reasonable representations of the modulating effect of instantaneous velocity. Ten males were observed performing trunk flexion and extension in the sagittal plane under constant load. Contraction velocities were measured as the first derivative from a devise sensitive to changes in spine curvature, and controlled by a visual feedback system while a constant load was applied through a chest harness. The erector spinae exhibited a yielding phenomenon which causes an abrupt drop in force during constant velocity stretching under constant, submaximal, stimulation. The findings were consistent with previous isovelocity muscle lengthening experiments. Yielding appeared dependent on the level of load/activation supporting the theory of a state-variableF/ relationship. The eccentric behaviour of the lower erectors (L3) seemed independent of velocity and length, while that of the upper erectors (T9) showed a dependence on length. At lower concentric velocities, concavity in torque-velocity curves was noted after a threshold velocity. The findings of this study strongly reinforce the notion that theF/ length relationship is not a continuous hyperbolic relationship during muscle shortening and that the commonly modelled force augmentation effect of lengthening is incorrect, at least for submaximal activation of the extensors of the lower back.     

Mycophenolate mofetil and tacrolimus as primary maintenance immunosuppression in simultaneous pancreas-kidney transplantation: initial experience in 50 consecutive cases

BACKGROUND: The current study examines the use of mycophenolate mofetil (MMF) and tacrolimus as primary immunosuppression in simultaneous pancreas-kidney (SPK) transplantation. In addition, analyses of the rates of conversion from one immunosuppressive agent to another, and its subsequent consequences with respect to outcomes were determined. Quality of graft function, infections, and effect on preexisting essential hypertension are also described. METHODS: Immunosuppression consisted of quadruple therapy with antithymocyte globulin induction, tacrolimus, MMF, and prednisone. Patient and graft survival and rejection rates in 50 consecutive SPK recipients, followed for a minimum of 3 months and a mean of 14 months (range: 3-34 months), are described. RESULTS: Thirty-nine of 50 (78%) patients tolerated the MMF/tacrolimus combination long-term (mean duration of follow-up: 14+/-7 months). Nine of 50 patients (18%) were converted to Neoral, and 4 patients were converted to azathioprine as a substitute for MMF. The 2-year actuarial patient, kidney, and pancreas survival rates were 97.7%, 93.3%, and 90.0%, respectively. At 6 months after transplant, the overall incidence of acute rejection was 16%. There was a statistically significant (P< or =0.04, Cox-Mantel test) difference in the rate of rejection associated with conversion to Neoral. The incidence of rejection 6 months after transplant in the group maintained on MMF/tacrolimus was 10.2% vs. 44.4% in the group converted to Neoral (P< or =0.04, Cox-Mantel test). Overall, the 1-year actuarial cumulative incidence of tissue-invasive cytomegalovirus disease was 6.6%. There were no cases of fungal infections or post-transplant lymphoproliferative disorders. One patient developed Kaposi's sarcoma 10 months after transplant. With respect to hypertensive disease, 60% (12/20) of the patients who required pharmacologic control of blood pressure before transplant were off all antihypertensive medications at 1 year after transplant. An additional 20% (4/20) of patients had a reduction in the number of medications required to control blood pressure at 1 year after transplant. CONCLUSIONS: We conclude that the combination of MMF and tacrolimus as primary immunosuppression for SPK transplantation results in excellent patient and graft survival rates, a very low rate of acute rejection, and low rates of infection and malignancy.     

Immunosuppression is not required for reactivation of latent murine cytomegalovirus

We have shown, for the first time, that TNF induces expression of MCMV IE RNA in the lungs of latently infected mice in the absence of immunosuppression. These initial data suggest that TNF may play an important role in the reactivation of latent MCMV, in the absence of immunosuppression, and provide a provocative insight into the mechanisms of CMV reactivation. Studies are in progress to determine whether genes associated with later stages of the viral life cycle are induced by TNF and whether infectious virus is produced.     

Transitional Cell Carcinoma Involving the Prostate with a Proposed Staging Classification for Stromal Invasion

Purpose

We investigated the effect on survival of transitional cell carcinoma of the prostatic urethra, ducts and stroma, and determined the difference between prostatic stromal involvement occurring via direct extension through the bladder wall versus stromal invasion arising intraurethrally.

Materials and Methods

Between August 1971 and December 1989, 489 men underwent radical cystoprostatectomy for transitional cell carcinoma, including 143 (29.2 percent) identified with prostate involvement by transitional cell carcinoma in the cystectomy specimen. Patients were separated into 2 groups: 1–19 in whom the primary bladder tumor extended full thickness through the bladder wall to invade the prostate (classified as P4a) and 2–124 in whom prostate involvement arose from within the prostatic urethra.

Results

Five-year recurrence-free and overall survival rates were 25 and 21 percent, respectively, in group 1 versus 64 and 55 percent, respectively, in group 2. In the 124 patients in group 2 survival rates were similar for those with prostatic urethral tumors or carcinoma in situ and ductal tumors (no stromal invasion). Five-year overall survival rates without and with stromal invasion were 71 and 36 percent, respectively (p less than 0.0001). Transitional cell carcinoma of the prostatic urethra or ducts does not alter survival predicted by primary bladder stage alone. Prostatic stromal invasion arising intraurethrally significantly decreases survival, which varies based on primary bladder stage (64.6 percent in stage P1, 30.8 percent in stages P2/P3a and 13.6 percent in stage P3b, p = 0.0001). P1 bladder tumors with prostatic stromal invasion arising intraurethrally had a significantly higher survival rate than P4a tumors (64.6 versus 21 percent, p = 0.0001). P3b bladder tumors with stromal invasion had a survival rate similar to that of P4a tumors (p = 0.78).

Conclusions

Prostatic urethral or ductal transitional cell carcinoma does not alter survival determined by primary bladder stage alone and it should not be classified as P4a. Prostatic stromal involvement arising intraurethrally significantly decreases survival predicted by primary bladder stage alone. P1 bladder tumors with prostatic stromal invasion arising intraurethrally have a significantly higher survival rate than P4a tumors and they should be separately classified as P1str. Muscle invasive (P2/P3a) bladder tumors with stromal invasion have a higher survival rate than P4a tumors (no statistical significance) and they should be designated separately (that is P2str). P3b bladder tumors with prostatic stromal invasion arising intraurethrally are indistinguishable from P4a tumors.     

A comparison of the haemodynamic effects of intrathecal meperidine,meperidine-bupivacaine mixture and hyperbaric bupivacaïne

Purpose

To study the haemodynamic effects of intrathecal meperidine, administered either alone or mixed with bupivacaïne.

Methods

We studied 42 Chinese patients, aged 59–87 yr, scheduled for transurethral bladder or prostate surgery, randomized into three equals groups, that received either meperidine 0.8 mg · kg^{?1 meperidine 0.4 mg} · kg^?1 plus 1.5 ml of 0.5% heavy bupivacaïne or 3 ml of heavy bupivacaïne 0.5%. Non-invasive systolic (SAP) and mean (MAP) arterial pressures, central venous pressure and cardiac index, stroke index and heart rate (HR) measured by the BoMed NCCOM3-R7S bioimpedance device, were recorded over the first 25 min. Systemic vascular resistance index (SVRI) was derived. Onset of sensory and motor block was also measured. Decreases in MAP of 25% were treated with colloid and metaraminol. Results: The onset of block was slower in the meperidine group (P < 0.05). Decreases in SAP, MAP and SVRI (all; P < 0.001) occurred within five minutes in all three groups. The HR was increased in the bupivacaïne group (P = 0.03), but bradycardias treated with atropine occurred in six patients receiving meperidine and four patients receiving the mixture. Six patients receiving meperidine and two patients receiving the mixture required general anaesthesia for inadequate block. The incidence of nausea and vomiting was higher in the patients receiving meperidine (P < 0.05). No other complications were encountered.

Conclusions

Intrathecal meperidine used alone or mixed with bupivacaïne has no intra-operative advantage over heavy bupivacaïne 0.5%.     

Progress in legal definition of brain death and consent to remove cadaver organs

E. coli endotoxemia affects hepatic energy linked function by uncoupling oxidation from phosphorylation. This study was done to determine whether a steroid, methylprednisolone sodium succinate (MPS), as well as excess substrate sodium succinate (SS), alters directly the effects of endotoxin on hepatic mitochondria. An assay system using alpha-ketoglutarate (alpha-Kg) was developed to test this hypothesis. Isolated rat hepatic mitochondria were first incubated in concentrations of MPS, ranging from 2.0 to 6.0 mg/ml. At these concentrations uncoupling identical to that occurring with addition of endotoxin resulted. However, a more dilute solution of MPS, 0.12 mg/ml, permitted normal mitochondrial function. Preincubation of MT in 0.12 mg/ml of MPS, as well as with sodium succinate, prevented endotoxin-induced uncoupling. Both endotoxin and steroid resulted in increased ATPase activity in the medium. While preincubation with MPS blocks the endotoxin effect, very high steroid concentrations alone are harmful. A direct action of steroids on mitochondria is evident, as well as a weaker protective effect due to excess substrate (alpha-Kg + SS). Since mitochondria are probably in direct communication with extracellular fluid, the assay system permits interaction of endotoxin, steroids, and substrates which mimic those which occur in vivo. The results of this study account for the previously reported variable effects obtained when steroids have been tested in vivo.