Rectal paracetamol has a significant morphine-sparing effect after hysterectomy

We have evaluated the morphine-sparing effect of rectal paracetamol during the first 24 h after abdominal hysterectomy in a placebo- controlled, double-blind study. We studied 72 patients receiving patient-controlled analgesia (PCA) with i.v. morphine after a standardized anaesthetic, allocated randomly to receive rectal paracetamol 1.3 g, diclofenac 50 mg or placebo, after wound closure and at 8 and 16 h. Suppositories were blinded by the hospital pharmacy. Study violations excluded data from seven patients. Patient data, morphine doses during anaesthesia and recovery, and sedation and nausea scores were comparable. Mean morphine consumption during PCA was 35.0 (SD 20.4) mg, 32.7 (27.4) mg and 54.9 (28.3) mg in the paracetamol (n = 24), diclofenac (n = 20) and placebo (n = 21) groups, respectively (P < 0.05). Morphine sparing during PCA for paracetamol and diclofenac (36% vs 40% over 24 h) was significant from 4 h. Global scores of average pain over 24 h were lower after diclofenac compared with paracetamol (P < 0.01) and placebo (P = 0.08). We conclude that rectal paracetamol was an efficacious adjuvant analgesic after regular dosing.      

Local recurrence has only a small effect on survival in high-risk extremity osteosarcoma

Background  

Tumor enlargement after chemotherapy is considered one of the high-risk factors for local recurrence and survival in osteosarcoma. We hypothesized patients with this risk factor will have similar survival regardless of the development of local recurrence.     

Factors which have a significant effect on the survival of human skin grafts.

Survival of 436 ABO-compatible skin grafts exchanged in 97 Caucasian families was prolonged if donor and recipient were genotypically, as compared with phenotypically, HLA identical. Among skin grafts between haploidentical family members, a mismatch at the A locus was equivalent to a mismatch at the B locus. Skin grafted from child to mother survived longer than did skin grafted between other family members, other variables being equivalent. A highly significant positive correlation was found between the age of recipient and skin graft survival. In addition, a significant interaction was found between the relationship of donor and recipient and degree of antigen match.     

Multifactorial intervention has a significant effect on diabetic kidney disease in patients with type 2 diabetes

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Metastatic breast cancer

The unfortunate reality of metastatic breast cancer is that all treatment is palliative in nature. This is a disease that currently has no cure and for which therapy is directed towards accentuating survival and relieving symptoms. Current technology allows the prediction and detection of metastases earlier and with greater accuracy. These achievements need to be consolidated by the discovery of innovative therapies that can alter the inevitable outcome of this disease.     

Adjuvant chemotherapy with doxorubicin and dacarbazine has no effect in recurrence-free survival of malignant phyllodes tumors of the breast

The purpose of this study was to evaluate the role of adjuvant chemotherapy in malignant phyllodes tumors of the breast treated at the Instituto Nacional de Cancerología of Mexico. Twenty-eight patients with malignant phyllodes tumors of the breast enrolled in a observational study from January 1993 to December 2003 to receive four cycles of adjuvant chemotherapy with doxorubicin 65 mg/m(2) over 48 hours intravenous infusion and dacarbazine 960 mg/m(2) over 48 hours intravenous infusion (n = 17) versus observation (n = 11). All patients had surgical resection, and 38% had an axillary dissection. Seven patients (25%) received adjuvant radiotherapy. Log-rank test was used to test for differences in recurrence-free survival (RFS). The median patient age was 42 years (range, 23-76 years). The median tumor size was 13 cm (range, 3-30 cm), and 46% of the tumors were in the left breast. At a median follow-up of 15 months (range, 2-81 months), there were seven recurrences and five deaths. The 5 year RFS rate was 58% (95% CI = 36% and 92%) for the patients who received adjuvant therapy and 86% (95% CI = 63% and 100%) for the patients who did not (p = 0.17). The median survival after recurrence was 6.5 months. Adjuvant chemotherapy with doxorubicin and dacarbazine did not affect patient survival. Future studies to identify relevant molecular targets should be implemented in order to define effective therapies for phyllodes tumors of the breast.     

High alcohol intake in deceased donors has no effect on pancreas graft survival: a registry analysis

Outcomes of pancreas transplantation from donors with high alcohol consumption are poorly described. The UK Transplant Registry was used to determine whether donor alcohol intake influenced pancreas survival in simultaneous pancreas–kidney (SPK) transplants performed between 2006 and 2012 (n = 770). Recipients were stratified by donor alcohol intake: group I (n = 122)—high recent alcohol intake (>21 or >14 units of alcohol/week in males or females, respectively) or previous alcohol abuse and group II (n = 648)—low/unknown current intake and no previous alcohol abuse. Median current alcohol intake was higher in group I than group II: 36.3 vs. 10 units/week; P < 0.001. One‐ and five‐year pancreas graft survivals were 88.5% and 73.6% in group I, and 87% and 74.9% in group II. There was no difference in unadjusted graft survival between groups I and II (P = 0.76), and no difference between group II and a subgroup of group I with a donor history of alcohol abuse and high current intake (P = 0.26), or from donors with current alcohol consumption of >50 units/week (P = 0.41). Pancreas donors with past alcohol abuse or current high intake are common, and graft outcomes appear to be acceptable. This analysis suggests that high donor alcohol intake, by itself, should not exclude consideration of pancreas transplantation.     

HA-1 mismatch has significant effect in chronic allograft nephropathy in clinical renal transplantation

BACKGROUND: The minor histocompatibility antigen HA-1 occurs in two allelic forms: H and R. The HA-1(H) form presented in the context of HLA A2 can elicit specific cytotoxic lymphocyte (CTL) responses and can cause graft-versus-host disease in marrow transplants. However, its significance in solid organ transplants is unknown. We determined whether incompatibility of the HA-1 resulted in enhanced rejection and whether HA-1 specific CTLs were generated. MATERIALS AND METHODS: HLA A2-matched donor/recipient pairs were selected and typed for HA-1 antigens by polymerase chain reaction. Nineteen of 81 pairs were mismatched for HA-1. Peripheral blood mononuclear leucocytes from five recipients, HLA A2 DR-matched with donors, were stimulated for 3 days with third-party donor, matched for HLA A2 DR but mismatched for HA-1. Cells were stained for surface markers, HA-1(H)-specific tetramer reagent, and analyzed by flow cytometry. Controls were unstimulated cells; PBML from two patients never exposed to HA-1(H); immunoglobulin G isotype-matched controls. For all patients, acute rejection rates posttransplant was ascertained. Long-term data was available for 36 patients. RESULTS AND CONCLUSIONS: There was no difference in acute rejection rates between the HA-1-matched and -mismatched groups, but there was a significant difference in chronic rejection rates, evidenced by increased graft failures during the follow-up period (P = .0024). Lymphocytes from five HA-1-mismatched recipients were stimulated in vitro with cells from HLA-A2 and DR-matched but HA-1-mismatched surrogate donor. Though there seemed to be an excess of tetramer-positive cells, anti-HA-1-specific CTL responses were not conclusively elicited in vitro.     

A modified fascia iliaca compartment block has significant morphine-sparing effect after total hip arthroplasty

We assessed whether a modified fascia iliaca compartment block in unilateral total hip arthroplasty provides a morphine-sparing effect in the first 24 hours. This involved a randomised, double blind study of 44 patients. Both groups received a modified fascia iliaca block with the trial group receiving 30 ml 0.5% bupivacaine with 1:200,000 adrenaline, 150 microg clonidine and 9 ml 0.9% saline and the control group receiving 40 ml 0.9% saline. Otherwise both groups received identical care with a subarachnoid block for operative anaesthesia. Patient-controlled morphine analgesia was commenced postoperatively and data were collected at three, six, 12 and 24 hours post commencement of surgery. We found that the trial group used less morphine at 12 and 24 hours (P < 0.001). The median morphine usage at 24 hours was 37.5 mg in the control patients and 22 mg in the trial patients. Pain scores were similar between groups. We conclude that a modified fascia iliaca compartment block has a significant morphine-sparing effect in unilateral total hip arthroplasty.     

Chronic use of the calcium channel blocker nifedipine has no significant effect on bone metabolism in men

Calcium channel blockers have been reported to have such diverse effects on reduction in protein synthesis, diminished incorporation of proline into new collagen, and decreased hormone release in vitro. The chronic affect of the calcium channel blocker nifedipine was examined in vivo to determine the possible impact of pharmacologic calcium channel blockade on bone metabolism. Eleven Caucasian males treated with an average of 40 mg/d nifedipine for an average of three years were compared to 11 control males matched for age, height, weight, activity level, cardiovascular status, and calcium intake. No significant differences between groups were noted in bone mineral density at the lumbar spine (L2-4), proximal femur (femoral neck, Ward's triangle and trochanter), and proximal and distal radius. There were also no significant differences in parameters of bone turnover (alkaline phosphatase, osteocalcin, urine calcium/creatinine, and hydroxyproline/creatinine ratio), or hormones that might affect calcium metabolism and bone (testosterone, PTH, 25(OH) vitamin D, and calcitonin). In summary, chronic nifedipine use in males is not associated with either a beneficial or adverse effect on bone metabolism.     

Anti-TNF antibody treatment has no positive effect on survival in a model of pneumococcal sepsis in pigs.

Gram-positive organisms causing sepsis have gained more significance in the past years. Especially patients with acquired immunodeficiency have been shown to be at risk for gram-positive infections. The mortality in Streptococcus pneumoniae bacteremia has been shown to be as high as 20%. Tumor necrosis factor-alpha (TNF-alpha) plays a crucial role in the "sepsis cascade." The previously described positive effect of monoclonal TNF antibody (anti-TNF-mAb) in gram-negative sepsis should be controlled in gram-positive pneumococcal sepsis. In a porcine model, pneumococcal sepsis was induced, and the course and outcome of a group treated with anti-TNF-mAb were compared to those of an untreated control. Streptococcus pneumoniae serotype 6 B was isolated from patients with systemic infection. The isolates were prepared, cryopreserved at -80 degrees C, and recultivated in a standardized fashion as needed. Then 10(9) bacteria were injected intravenously. Pigs of the German Landrace type with a weight of 20-30 kg were anesthetized using standardized midazolam and ketamine intravenous anesthesia. After introduction of central venous, arterial, and urinary catheters, bacteria were injected intravenously via the ear vein. In the therapy group, animals were treated with anti-TNF-mAb (5 mg/kg body weight) intravenously immediately prior to pneumococci injection. Survival and survival times were primary endpoints. Biochemical and vital parameters were also compared. In the anti-TNF-mAb group, 4/11 animals died (35%), compared to 6/11 (55%) in the control group. The mean survival times were 11 and 10 h, respectively (n.s.). TNF levels were significantly different. The TNF peak at 90-240 min was not present in the anti-TNF group (340 pg/ml vs. 19 pg/ml, p = .034). Leukocyte counts differed also significantly. After an initial drop in both groups, we observed a leukocytosis of up to 32.8 +/- 5.0 g/L in the anti-TNF-group, while in the control group leukocyte counts remained below 15.0 g/L (13.3 +/- 3.0 g/L, p = .007). All other parameters did not differ significantly. Thus, anti-TNF-mAb effectively suppresses the TNF peak following gram-positive septicemia. In the presented setting, these effects did not influence overall survival or survival times.     

Periodic follow-up after breast cancer and the effect on survival.

OBJECTIVE: To assess the role of routine follow-up in current management of breast cancer. DESIGN: Retrospective review. SETTING: Teaching hospital, The Netherlands. SUBJECTS: 270 patients who presented with recurrent breast cancer, 1974-90. MAIN OUTCOME MEASURE: Recurrence was coded as asymptomatic or symptomatic and related to survival. RESULTS: 170 (63%) of the recurrences were detected when they were symptomatic and 100 (37%) when they were not. The groups differed significantly according to the site of recurrence; 45/100 recurrences were local in the asymptomatic group compared with 23/170 (14%) in the symptomatic group. There was no significant difference in disease-free survival between the two groups. Overall 5-year survival after primary treatment for all recurrences (locoregional and distant) was significantly better (p=0.0003) in the asymptomatic group (62/100) than in the symptomatic group 79/170 (46%). However, when locoregional and distant recurrences were analysed separately no significant differences were found between both groups in overall survival after primary treatment or survival after detection of recurrence. The 5-year overall survival after primary treatment for distant recurrence was 26/47 (55%) in the asymptomatic group compared with 62/134 (46%) in the symptomatic group (p=0.13). For locoregional recurrence these figures were 35/45 (78%) and 14/23 (61%), respectively (p=0.34). Routine follow-up hardly affected the course of locoregional recurrence. Only five of 75 patients with local recurrence (7%) developed uncontrolled local disease, 2 of whom were initially detected during routine follow-up. CONCLUSIONS: We conclude that in the current management of breast cancer the medical impact of follow-up is low, so follow-up visits after treatment for breast cancer are hardly warranted.     

Omission of surgery in older women with early breast cancer has an adverse impact on breast cancer‐specific survival

Background

Primary endocrine therapy is used as an alternative to surgery in up to 40 per cent of women with early breast cancer aged over 70 years in the UK. This study investigated the impact of surgery versus primary endocrine therapy on breast cancer‐specific survival (BCSS) in older women.

Methods

Cancer registration data for 2002–2010 were obtained from two English regions. A retrospective analysis was performed for women with oestrogen receptor (ER)‐positive disease, using statistical modelling to show the effect of treatment (surgery or primary endocrine therapy) and age and health status on BCSS. Missing data were handled using multiple imputation.

Results

Cancer registration data on 23 961 women were retrieved. After data preprocessing, 18 730 of 23 849 women (78·5 per cent) were identified as having ER‐positive disease; of these, 10 087 (53·9 per cent) had surgery and 8643 (46·1 per cent) had primary endocrine therapy. BCSS was worse in the primary endocrine therapy group than in the surgical group (5‐year BCSS rate 69·4 and 89·9 per cent respectively). This was true for all strata considered, although the difference was less in the cohort with the greatest degree of co‐morbidity. For older, frailer patients the hazard of breast cancer death had less relative impact on overall survival.

Conclusion

BCSS in older women with ER‐positive disease is worse if surgery is omitted. This treatment choice may contribute to inferior cancer outcomes. Selection for surgery on the basis of predicted life expectancy may permit choice of women for whom surgery confers little benefit.     

Maintaining blood pH at 7.4 during hypothermia has no significant effect on work of the isolated rat heart

Variation in the pH of biologic fluids parallels modifications in the neutral point of water, which is temperature dependent. Therefore, pH adjustment, when organs from homeotherms are subjected to hypothermia as presently practiced in cardiac surgery or organ preservation, appears to be justified. The present study evaluated, during moderate hypothermia (26 degrees C), the effect of variations in perfusate pH on hemodynamic performance of isolated working rat hearts in conditions of increased workload. Perfusates of blood with a pH corrected according to the pH-temperature relationship of neutral water, and blood with pH maintained at 7.4 were used. Hemodynamic function was unaltered by respiratory modifications in blood pH (normal pH blood: pH = 7.59 +/- 0.01; PCO2 = 20 +/- 1 mmHg; blood maintained at pH 7.4: pH = 7.39 +/- 1; PCO2 = 37 +/- 1 mmHg) and the hypothermic heart perfused with blood at pH 7.4 maintained its ability to do work in response to increased workload. The authors conclude that isolated heart at this degree of hypothermia has the capacity to resist noticeable changes in blood pH with no deleterious effect on its functional characteristics even at high workloads. The results suggest that the range of optimum extracellular pH value is relatively large at a given temperature. Such good tolerance could be related to tissue buffering efficiency and no conclusion concerning the relationship between tolerance of cellular function and intracellular pH changes can be made.