Jacob Hart

Effects of anesthesia based on large versus small doses of fentanyl on natural killer cell cytotoxicity in the perioperative period.

Surgical stress and general anesthesia suppress immune functions, including natural killer cell cytotoxicity (NKCC).This suppression could be attributable, at least in part, to opiates. We have previously shown that large-dose fentanyl administration suppressed NKCC in rats. The present study sought to compare the effects of two anesthetic protocols, based on large-(LDFA) versus small (SDFA)-dose fentanyl anesthesia on NKCC in the perioperative period. Forty patients were included in this study; half were assigned to each protocol of anesthesia. In each anesthetic group, half the patients were undergoing surgery for malignant diseases, and half for benign conditions. Blood samples were collected during the perioperative period. NKCC was assessed using the chromium release assay. Initially, both types of anesthesia similarly suppressed NKCC, with a peak effect 24 h after surgery. The two types of anesthesia, however, differed in the rate of recovery of NKCC suppression. By the second postoperative day, NKCC returned to control values in the SDFA patients, whereas NKCC was still significantly suppressed after LDFA. These results indicate that LDFA causes prolonged suppression of NK cell function. Whether this suppression might have a long-term impact on the overall outcome, especially in cancer patients, remains to be determined. (Anesth Analg 1996;82:492-7)

On the meaning of fragile sites in cancer risk and development.

In the last few years, there has been increasing concern about the possible involvement of fragile sites in cancer risk and development. Patients with malignancies and family histories of cancer who presented with constitutional fragile sites are reported here. These findings are discussed with regard to the familial risk for cancer and the tissue specificity of the malignancy in relation to the different fragile sites. The hypothesis is advanced that these may be sites of viral DNA modification, probably representing areas where genes that are important for the metabolism of the virus are located. On the other hand, these genes may well be cellular (proto)oncogenes. We believe that fragile sites may increase the risk for cancer, not by being break-prone points at oncogene locations, but through more complex mechanisms that are not easy to predict.

Cytogenetic study of patients with carcinoma of the colon and rectum: particular C-band variants as possible markers for cancer proneness

A possible involvement of chromosomal heterochromatic polymorphisms in propensity to cancer has been considered and discussed by several investigators who studied groups of patients presenting with different forms of malignancy. We report a cytogenetic study on the circulating lymphocytes of patients suffering from colorectal carcinoma, most of whom were of European origin. Significantly increased incidence of polymorphisms of chromosomes #1 and #9 was found, especially partial inversions (PI). Emphasis is given to the problem of selecting adequate controls, which must be as homogeneous as possible.

The Correlation of Increased Serum Prolactin Levels with Decreased Sexual Desire and Activity in Elderly Men

Serum prolactin levels and sexual function were evaluated in 28 men from 60 to 64 years of age and in 44 men from 65 to 70 years of age. All subjects were married, physically healthy, and had no psychopathology or marital problem. About a third of the men aged 60 to 70 years suffered from impotence. No obvious correlation between elevated levels of serum prolactin and impotence was obtained. Subjects aged 65 to 70 who had decreased libido exhibited a significant elevation of serum prolactin levels, while subjects of the same age group who had reserved (normal) libido appeared to have low serum prolactin levels. Nine of ten men aged 60 to 70 years with serum prolactin levels above 40 ng/ml reported decreased libido. Potent men of both age groups (60–70 years) with high prolactin levels showed a tendency to have a decrease in frequency of sexual intercourse. Thus, it seems that mild hyperprolactinemia in aging men may be associated with decreased sexual desire and frequency of sexual activity.

Human colostrum stimulates cytokine production.

The effect of human colostrum on the production of IL-1, IL-3 and IL-6 by peripheral blood mononuclear cells (PBMCs) has been investigated. The aqueous phase of human colostrum significantly stimulated the production of these three cytokines. These findings show the importance of breast feeding not only as a well-balanced nutrient supply but also as a source for growth-promoting factors. It is suggested that the enhanced secretion of IL-1, IL-3 and IL-6 induced by human colostrum may compensate for the lower capacity of neonatal PBMCs to produce these cytokines. It is also possible that, by stimulating the secretion of these cytokines, breast feeding may provide an additional mechanism for the regulation of the neonatal immune system and hematopoiesis.

A new familial "fragile site" on chromosome 16 (q23-24). Cytogenetic and clinical considerations

SummaryA new familial fragile site at 16q23-24 is documented, and the clinical and cytogenetic data on three families and some individual patients are reported. The importance of differentiating this fragile site from that recognized previously at 16q22 is pointed out.

Peripheral-type benzodiazepine receptor ligands modulate human natural killer cell activity

Following our earlier work, we evaluated the in vitro effect of ligands active at the peripheral-type benzodiazepine receptors on human natural killer cell activity. Peripheral blood mononuclear cells were incubated with benzodiazepine receptor ligands. After 4 h we observed a nonspecific inhibition of natural killer cell activity induced by both peripheral (Ro5-4864 and PK 11195) and central (clonazepam) benzodiazepine receptor ligands; after 24 h, the suppressive activity was specific to peripheral and mixed (diazepam) ligands, and the central-type ligand had no effect. This significant, specific suppression of NK cell activity was completely reversed by the addition of human recombinant interleukin-2 or human leukocyte interferon. Our research provides additional information on the immunomodulatory effects of peripheral-type benzodiazepine ligands. Further studies are needed to clarify the underlying mechanism of natural killer cell inhibition and to determine the clinical implications of these findings.

Oral Contraceptive Use and BRCA Penetrance: A Case-Only Study

Background: Women with deleterious mutations in BRCA genes are at increased risk of breast cancer. However, the penetrance of the genetic trait may be regulated through environmental factors. This multinational case-only study tested the interaction between oral contraceptive use and genetic susceptibility in the occurrence of breast cancer. Methods: We recruited 3,123 patients diagnosed with breast cancer before the age of 45 years. Participants were classified according to their probability of carrying a BRCA mutation on the basis of their family history of breast and ovarian cancer. According to a case-only approach, the frequency of relevant exposures among breast cancer cases with high probability of BRCA mutation (“genetic cases”) was compared with the frequency of the same exposures among breast cancer cases with a low probability of BRCA mutation (“sporadic cases”). The interaction odds ratios (OR) and 95% confidence intervals (CI) for oral contraceptive use were estimated by unconditional logistic regression, after controlling for potentially confounding variables. Results: The analysis was carried out comparing 382 “genetic” and 1,333 “sporadic” cases. We found a borderline significant interaction between genetic breast cancer and oral contraceptive use for ever users compared with never users (OR, 1.3; 95% CI, 1.0-1.7). The greatest interaction OR was found for women who started using pill at 18 to 20 years (OR, 1.6; 95% CI, 1.1-2.3). Conclusion: These results suggest that BRCA mutation carriers, as well as women with a significant family history of breast and ovarian cancer are more vulnerable to exogenous hormones in oral contraceptives. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2107–13)

Vincristine-induced alterations in Schwann cells of mouse peripheral nerve.

The sciatic nerve of C57Bl mice was examined with a transmission electron microscope to study the ultrastructural alterations in Schwann cells following treatment with escalating doses of vincristine. Results indicated that the drug exerts a dose‐related effect. Total doses up to 8 µg/mouse did not cause any visible damage to Schwann cells. Higher doses induced not only damage to individual cells, but also affected a greater percentage of them. The myelin sheath was the most affected organelle. Schwann cells of myelinated fibers showed greater damage than those of unmyelinated fibers.

Familial fragile site found at the cancer breakpoint (1)(q32)

SummaryA normal baby was cytogenetically examined immediately after birth for the possible presence of a fragile (16)(q22), which had been found in her mother and in her retarded sister with a 46,XX;46,XX,del(16)(q22) mosaic karyotype. Distamycin a was added to the cultures to enhance the fragile (16)(q22) expression. The response of the baby to the action of distamycin a in vitro was much greater than that of her family members. A fragile (16)(q22) was induced in many cells as well as a fragile (1)(q32), which was also found in her mother. This fragile site, which is known to be a cancer breakpoint, has not been reported so far either to be familial or to be inducible by distamycin A. The concomitance of fragile (1)(q32) with fragile (16)(q22) and their possible significance are considered.