Sources of antibody-dependent cellular cytotoxicity deficiency in young pig leukocytes.

Antibody-dependent cellular cytotoxicity (ADCC) activity against pseudorabies virus-infected target cells has been found to be lower in young pig peripheral blood leukocytes (PBLs) than in adults. Experiments were designed to investigate the reason(s) for low activity in the young, which are more at risk of fatal infection than adults. The percentage of polymorphonuclear leukocytes (PMNs), the major ADCC effector cell, in the whole leukocyte population did not have a bearing on the deficiency. Enrichment for PMNs did not alleviate differences in activity between young and adult pigs. Additionally, no suppressor cell(s) or factor(s) could be demonstrated to account for the ADCC deficiency. The source of the ADCC deficiency in the young was found to be related to the decreased ability of young pig effector cells to bind antibody-sensitized targets. This deficiency relative to adults was associated with decreased antibody binding to high affinity Fc receptors on young pig neutrophils.     

Langzeitergebnisse der Kontinenzfunktion nach ileoanaler Pouch-Anlage

An important aim of proctocolectomy with ileal pouch-anal anastomosis (IPAA) is to maintain anal continence. Anal sphincter disruption during IPAA is felt to play an important role in loss of continence, which is described in up to 30% of the treated patients in the early postoperative period. Although sphincter function recovers gradually after surgery, some patients stay incontinent. In our investigation of possible parameters involved in preservation of continence after this operative procedure, we focused on changes in anal manometry. We compared these findings with the functional results obtained by questioning the patients and physical examination. Anal manometry was performed with a low-compliance hydraulic perfusion system. All patients underwent a J-pouch procedure with a short rectal cuff for ileoanal reconstruction. We examined 25 patients, 13 underwent operation for the treatment of ulcerative colitis, 12 because of adenomatous polyposis. In the colitis and polyposis group, 28% of the patients reported events of soiling. Three patients (12%) were incontinent. The remaining 15 patients were completely continent. The median time after operation was 58 months, ranging from 12 to 96 months. Comparing the results of anal manometry with standard values of ten age- and gender-matched healthy volunteers, it was found that there was a significant increase in the threshold of balloon awareness and urge to defecate. These sensations were sometimes elicited by pouch contractions. Median pouch- compliance was also clearly elevated in comparison to rectal compliance (P<0.005). Inhibitory reflexes during balloon inflation could not be evoked in any of the patients. Comparing continent with incontinent patients there were significant differences in balloon awareness, urge to defecate, and stool frequency (P<0.01,P<0.01 andP<0.001, respectively). But in contrast to other publications, we could not find significant differences in anal sphincter length, resting and squeezing, anal canal pressure. Pouch compliance was lowered in incontinent patients and negatively correlated with stool frequency (P<0.001,r=?0.82). In conclusion, our study indicates that anal sphincter resting pressure alone is not a crucial factor in continence preservation in the long-term after total proctocolectomy and IPAA. Poor pouch- compliance and concomitant higher stool frequencies seem to be related to incontinence in this patient group.     

Update on treatment of pediatric pain with surgical considerations

The assessment, treatment, and prevention of pediatric pain pose a special challenge to surgeons and others involved in the care of children. The experience of pain is subjective, and infants and many children are unable to verbalize their level of discomfort. Therefore, it is the responsibility of physicians and nurses to be educated and trained to identify nonverbal signs of pain and discomfort, anticipate the experience of pain associated with specific procedures and diagnoses, and initiate the appropriate use of analgesics as well as nonmedicinal strategies to relieve this pain.     

Indwelling epidural catheters for pain control in gynecologic cancer patients

Seven patients with severe pain caused by an advanced, incurable gynecologic malignancy were treated with an indwelling epidural catheter connected to an implantable subcutaneous port through which morphine was infused. There were few major complications associated with insertion or maintenance of the system. The average usage was 60 days, although the system functioned continuously for 6 months in one patient. Pain distribution in these women ranged from the upper abdomen to the lower extremities. All patients, including one with liver metastases, reported good to excellent pain control with the epidural narcotics. Two subjects with upper abdominal pain occasionally required supplemental oral oxycodone, but the other five patients had adequate pain relief with the epidural system alone. The indwelling epidural system provides excellent analgesia for patients with advanced, incurable gynecologic cancer.     

Lower heat shock factor activation and binding and faster rate of HSP-70A messenger RNA turnover in heat sensitive human leukemias.

Normal bone marrow progenitors and some leukemic cells develop only a limited amount of thermotolerance. Further, once developed, thermotolerance decays at a faster rate than that normally observed in cells of nonhemopoietic origin. Thermotolerance induction and maintenance correlates with reduced levels of expression of various M(r) 70,000 heat shock proteins (HSP-70) mRNAs after heat shock. We have now compared the accumulation of HSP-70 proteins in heat-shocked human leukemic cells KG-1, HL-60, and K562 to that in Ht1080, a colon carcinoma cell line. We have found reduced accumulation of HSP-70 proteins in all leukemic cells. The rate of decay of HSP-70A mRNA, measured following heat shock by using actinomycin D treatment to inhibit further RNA synthesis, was more rapid in KG-1 and HL-60 cells compared to Ht1080 cells. The half-life of HSP-70A mRNA was 2 h in KG-1 and HL-60 cells while in Ht1080 cells it was > 7 h. HSP-70A mRNA is known to decay with a half-life of 2 h in unheated cells; this is increased to > 7 h following heat shock. We therefore postulate that leukemic cells lack the mechanism to stabilize HSP-70A mRNA after heat shock. One postulated mechanism for HSP-70 mRNA decay rate is known to be due to the nucleotide sequences at the 3'-untranslated region. We examined the 3'-untranslated region in leukemic cells. No sequence variations, however, were observed at either the genomic or the complementary DNA levels between leukemic or nonleukemic tumor cells. Heat shock factor activation and binding by gel retardation assays showed that KG-1 and HL-60 cells had a reduced heat shock factor binding to the heat shock element when compared to K562 and Ht1080 cells. Furthermore, HSF-1 mRNA was found to be expressed at relatively lower levels in HL-60 cells when compared to Ht1080 or KG-1 cells. In conclusion, reduced HSP synthesis and accumulation of leukemic cells after heat shock correlates with the reduction in heat shock factor-heat shock element binding and a faster HSP-70A mRNA decay rate that is observed in these cells.     

Effect of N-alpha-methyl histamine on ulcer healing in rats

Inflammation Research -