9-cis-Retinoic acid suppresses mammary tumorigenesis in C3(1)-simian virus 40 T antigen-transgenic mice.

Retinoids have been investigated as potential agents for the prevention and treatment of human cancers. These compounds play an important role in regulating cell growth, differentiation, and apoptosis. 9-cis-Retinoic acid (9cRA) is a naturally occurring ligand with a high affinity for both the retinoic acid receptors and the retinoid X receptors. We hypothesized that treatment with 9cRA would prevent mammary tumorigenesis in transgenic mice that spontaneously develop mammary tumors. To test this hypothesis, C3(1)-SV40 T antigen (Tag) mice, which develop mammary tumors by the age of 6 months, were treated daily p.o. with vehicle or two different dose levels of 9cRA (10 or 50 mg/kg) from 5 weeks to 6 months of age. Tumor size and number were measured twice each week, and histological samples of normal and malignant tissue were obtained from each mouse at time of sacrifice. Our results demonstrate that 9cRA suppresses mammary tumorigenesis in C3(1)-SV40 Tag-transgenic mice. Time to tumor development was significantly delayed in treated mice; median time to tumor formation for vehicle-treated mice was 140 days versus 167 days for mice treated with 50 mg/kg 9cRA (P = 0.05). In addition, the number of tumors per mouse was reduced by >50% in mice treated with 9cRA (3.43 for vehicle, 2.33 for 10 mg/kg 9cRA, and 1.13 for 50 mg/kg 9cRA, P < or = 0.002). Histological analysis of the mammary glands from vehicle and treated mice demonstrated that 9cRA treatment also did not affect normal mammary gland development. Immunohistochemical staining of normal and malignant breast tissue and Western blot analysis demonstrated that SV40 Tag expression was not affected by treatment with retinoids. Single doses of 10 and 50 mg/kg resulted in peak plasma concentrations of 3.4 and 6.71 microM, respectively. Daily doses of 9cRA for 28 days resulted in plasma concentrations of 0.86 and 1.68 microM, respectively, concentrations consistent with that seen in humans treated with 9cRA in clinical trials. These results demonstrate that 9cRA suppresses mammary carcinogenesis in transgenic mice without any major toxicity and suggest that retinoids are promising agents for the prevention of human breast cancer.

Immunologic response to different determinants of benzylpenicillin, amoxicillin, and ampicillin. Comparison between urticaria and anaphylactic shock.

BACKGROUND: Subjects with IgE-mediated allergic reactions to penicillins can develop urticaria or anaphylactic shock. Urticaria is mainly associated with positivity to the major determinant of benzylpenicillin (BPO), and anaphylactic shock with minor determinants (MDM). The presence of IgG antibodies to BPO is thought to be mainly associated with urticaria, possibly protecting from anaphylactic shock. We aimed to study the skin test response to BPO and MDM, amoxicillin (AX), and ampicillin (AMP) in a group of subjects allergic to penicillins, and to evaluate the role of specific IgG. METHODS: We studied a group of patients with immediate allergic reactions to penicillins, comparing urticaria and anaphylactic shock. Skin tests were done with BPO, MDM, AX, and AMP. Specific IgE and IgG antibodies to benzylpenicilloyl-poly-L-lysine (BPO-PLL) and amoxicilloyl-poly-L-lysine (AXO-PLL) were determined by RAST and ELISA, respectively. RESULTS: Fifty-nine patients were studied (30 with anaphylactic shock and 29 with urticaria). Skin test positivity to BPO was associated with urticaria (P<0.001), and positivity to MDM, AX, and AMP with anaphylactic shock (P=0.006, P<0.001, and P=0.002, respectively). Specific anti-BPO-PLL and AXO-PLL IgG values were higher in patients than controls (P<0.001), but no differences were observed between urticaria and anaphylactic shock. CONCLUSIONS: Positivity to minor determinants of penicillins is associated more with anaphylactic shock than urticaria, but the role of IgG antibodies in helping to prevent the development of anaphylactic shock could not be confirmed.

Prehospital classification combined with an in-hospital trauma radio system response reduces cost and duration of evaluation of the injured patient.

BACKGROUND: This study was undertaken to determine whether a prehospital trauma classification system (PHTCS) in combination with an in-hospital trauma radio system response (IHTRSR) impacts emergency care of the injured patient. METHODS: In 1991 our trauma center used no prehospital trauma classification system. A PHTCS was implemented in 1992, and in 1993 the PHTCS was integrated with an IHTRSR: RESULTS: Implementation of the PHTCS and IHTRSR resulted in a significant reduction in the time required for initial evaluation of the trauma patient with an associated reduction in cost. Reduction in time of the initial trauma evaluation was noted in both adult and pediatric populations, in patients with a blunt mechanism of injury, and in the injured patients posing the greatest strain to health care resources. CONCLUSIONS: Integration of a PHTCS with an IHTRSR has a significant impact on the cost and time of emergency treatment of the trauma victim with no adverse effect on patient outcome. Use of an integrated trauma response provides cost-effective and expeditious care of the injured patient and should be considered in trauma system development.

The effect of essential fatty acid supplementation on keratinocyte replication.

Epidermal cell growth in culture, using the low calcium, low serum technique described by Boyce, is thought to induce rapid expansion by inducing an essential fatty acid (EFA) deficiency state. To determine the mechanisms whereby EFA deficiency induces increased epidermal cell growth, keratinocytes were passaged into medium without or with the addition of EFAs, 18:2(n-6), 20:4(n-6). The resulting populations were assayed for replication rate, differentiation, and plating efficiency. Supplemental EFAs significantly decrease keratinocyte culture expansion. This is evidenced by an increase in generation time, a decrease in thymidine incorporation, and a decrease in modeled replication rate. EFA supplementation also increased the expression of cornified cell envelopes. Serum-free medium induces EFA deficient keratinocytes that demonstrate increased replication and decreased differentiation. Restoration of EFAs reverses these changes. It may be possible to manipulate keratinocyte physiology using fatty acid modifications.

[Anisakiasis as a cause of acute appendicitis and rheumatologic picture: the first case in medical literature]. / Anisakiasis como causa de apendicitis aguda y cuadro reumatológico: primer caso en la literatura médica.

We report a case of acute abdomen due to appendicular lumen occlusion by anisakis larvae. This is the first case of human anisakiasis known in Spain, and the first case of acute appendicitis, in the medical World literature, produced by this nemathode. The association of myalgias and arthralgias stands out, being in this aspect the second case found the in medical litterature.