Cyclical use of tamoxifen and high-dose medroxyprogesterone acetate in advanced estrogen receptor positive breast cancer

Summary One-hundred and seventy patients with estrogen receptor positive (10 pmol/g protein) advanced breast cancer have been treated in a prospective randomized study either with continuous tamoxifen 30 mg × 1 daily (TAM), or with TAM 30 mg × 1 daily for 8 weeks alternating with medroxyprogesterone acetate 500 mg × 2 daily for 8 weeks (TAM/HD-MPA). The response rate was 62% in the group treated with cyclic TAM/HD-MPA versus 41% in the TAM alone group (p = 0.02). There was no significant difference in duration of remissions or survival.     

Somatic nerve stimulation and cholera-induced net fluid secretion in the small intestine of the rat: evidence for an opioid effect

The effects of somatic nerve stimulation on cholera toxin induced secretion was investigated in vivo in anaesthetised rats. Small intestinal secretion was induced with cholera toxin and measured by a gravimetric technique. Afferent stimulation (pulse frequency within train; 100 Hz; train duration: 50 ms; train frequency: 3 Hz) of the sciatic nerve over 30 min significantly reduced the net fluid secretion both during (P < 0.05) and after cessation of the stimulation (P < 0.01). The greatest effect was obtained immediately after the termination of the nerve stimulation when the secretion was reversed to net fluid absorption. The opioid receptor antagonist naloxone (10 mg kg(-1) i.v.) administrated during the stimulation, significantly inhibited the antisecretory effect seen after the stimulation, thus no significant difference was seen between the control period and the periods after cessation of the stimulation. The opioid receptor antagonist naloxone methiodide (10 mg kg(-1) i.v.), which does not cross the blood-brain barrier, partly inhibited the antisecretory effects but not with the same magnitude as naloxone, thus the net fluid secretion was still significantly inhibited after the stimulation (P < 0.05). We conclude that afferent stimulation of the sciatic nerve strongly inhibits the cholera toxin induced secretion in the small intestine. This inhibition involves primarily a central opioid mechanism and to a lesser extent peripheral opioid mechanism.     

FIELD TRIAL OF Bacillus thuringiensis var israelensis PELLET FORMULATION IN THE CONTROL OF MOSQUITOES

In a simulated field trial Bacillus thuringiensis var israelensis (BTI) pellet formulation exhibited an enhanced efficacy with increasing dose. A dosage of 1.0 and 1.5 ppm was most effective under simulated field conditions. In field trials persistence of BTI pellet (1.0 ppm) was observed for 35 days in moderately polluted water collection as compared to 21 days in highly polluted water bodies.KEY WORDS: Bacillus thuringiensis, Malaria, Mosquito control     

Gender and Ethnic Differences in Survival in a Cohort of HIV Positive Clients

Objectives: The purpose of this study was to examine gender and ethnic differences in survival of persons receiving treatment for HIV infection to determine if differences existed, and if they did, to assess the possibility of explaining these differences by examining other factors, such as age, disease severity when beginning treatment, alcohol, illicit drugs, tobacco, educational level, living arrangements, antiretroviral treatment, PCP prophylaxis, sexually transmitted diseases, mode of transmission and opportunistic infections.

Design: A retrospective cohort study of all clients receiving treatment at an HIV only clinic from its opening in early 1988 until the end of May 1993. Statistical methods used to examine the data included incidence density ratios, Kaplan‐Meier survival curves, Breslow (generalized Wilcoxon) tests of equality of survival curves and Cox proportional hazards models both with and without time dependent covariates.

Results: In the cohort (37% African American, 7% Hispanic American and 25% female), 220 deaths occurred during 1223 person years of follow‐up. Compared to European American males, the following incidence density ratios were observed: European American females: 0.50, Hispanic American females: 0.70, Hispanic American males: 0.96, African American females: 1.28 and African American males: 2.38. The differences were noted above for gender/ethnicity groups were significant at the p < 0.0001 level. After adjusting for disease stage (as measured by laboratory testing of CD4 positive T‐lymphocytes), educational level, and age, no differences in survival by gender or ethnicity remained. Disease stage and educational level had the greatest prognostic significance.

Conclusions: European Americans entered treatment at a much earlier disease stage (as measured by CD4 positive T‐lymphocyte counts) and had higher educational levels (a surrogate for socioeconomic status) than African Americans. These factors may explain the longer survival in European Americans as compared to African Americans in this cohort.     

Laminin-5 γ2-chain expression and DNA ploidy as predictors of prognosis in endometrial carcinoma

Expression of the laminin-5 γ2-chain in carcinoma cells has been implicated in tumor invasion. The aim was to investigate the expression and prognostic significance of the In-5 γ2-chain compared with clinicopathological factors and tumor cell DNA ploidy in endometrial carcinoma. Histological specimens from 80 endometrial carcinomas were examined with respect to immunohistochemical In-5 γ2-chain expression and correlated to the clinicopathological characteristics, DNA ploidy, and survival. Sixty-eight of 80 investigated cases were judged to be positive for the In-5 γ2-chain. Ln-5 γ2-chain did not show any correlation to stage, histopathological subtype, grade, and DNA ploidy. In univariate analyses, advanced stage (p<0.001), nonendometrioid carcinoma (p=0.030), low grade (p<0.001), aneuploid tumors (p<0.001), and In-5 γ2-chain expression (p=0.017) were highly associated with poor survival. Aneuploid tumors in combination with strong In-5 γ2-chain expression were significant predictors (p<0.001) of poor prognosis. In multivariate analyses including stage, histopathological subgroup, grade, DNA ploidy, and In-5 γ2-chain expression, all lost their significant prognostic information except for stage (p<0.001) and grade (p<0.05). Ln-5 γ2-chain expression and DNA ploidy both as a single parameter and in combination were demonstrated to be significant prognostic factors in univariate analysis. However, stage and grade provided more useful clinical information beyond histopathological subgroup, DNA ploidy, and In-5 γ2-chain expression. The results also indicate that In-5 γ2-chain expression is upregulated during the progression of endometrial carcinoma.     

New non-cocaine-containing topical anesthetics compared with tetracaine-adrenaline-cocaine during repair of lacerations

OBJECTIVE: To compare the effectiveness of three new topical anesthetics that do not contain cocaine (prilocaine-phenylephrine, tetracaine-phenylephrine [tetraphen], and tetracaine-lidocaine-phenylephrine) to that of tetracaine-adrenaline-cocaine (TAC) during laceration repair in children. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: The emergency department of an urban children's hospital. PARTICIPANTS: Children 1 year of age or older with a laceration /= 5 years of age using a visual analogue scale (VAS). Suture technicians, research assistants, and parents also scored pain using a seven-point Likert scale. In addition, suture technicians completed an anesthetic effectiveness scale. RESULTS: There was consistently no difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. A statistically significant difference was seen among anesthetics when comparing VAS and Likert scale scores of suture technicians and Likert scale scores of research assistants. Based on post hoc analyses, these statistically significant differences were between TAC and prilocaine-phenylephrine (suture technician VAS and Likert scale) and between TAC and tetracaine-lidocaine-phenyl-ephrine (suture technician Likert scale), but not between TAC and tetraphen. When power analyses were performed using alpha = 0.05 and beta = 0.20, it was possible to detect a difference of 1.2 VAS units for each of the observer groups. Based on anesthetic effectiveness scale scores, the three new topical preparations collectively performed significantly better on the face and scalp than on the extremities (relative risk = 1.83; 95% confidence interval 1.20 < relative risk < 2.79). CONCLUSION: This study demonstrated the effectiveness and safety of three new non-cocaine-containing topical anesthetics. Consistently, there was no statistical difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. Tetraphen offers an effective alternative to TAC during laceration repair in children.     

Hypospadias trends in two US surveillance systems

OBJECTIVE: Hypospadias is a common congenital anomaly, the cause of which is unknown. Unexplained increases in the rates of hypospadias occurred in five European countries in the 1970s and 1980s. We examined data from two birth defects surveillance systems in the United States for evidence of similar trends. METHODOLOGY: The Metropolitan Atlanta Congenital Defects Program (MACDP) provided birth prevalence rates from 1968 to 1993. The nationwide Birth Defects Monitoring Program (BDMP) provided rates from 1970 to 1993. MACDP data are population-based and could be categorized by the severity of the hypospadias. BDMP data allowed analysis of rate trends for the four census regions of the United States. RESULTS: Data from both surveillance systems showed an approximate doubling of hypospadias rates in the 1970s and 1980s. MACDP data showed that the rate of severe cases increased while the ratio of mild to severe cases decreased. BDMP data showed that hypospadias rates increased markedly in all four regions of the United States. CONCLUSIONS: The observed increases are unlikely to be attributable to increased sensitivity of the surveillance systems or the identification of more mild cases by physicians over time, because either trend would have increased rather than decreased the ratio of mild to severe cases. If real, these trends represent the largest number of cases and the first report of an increase in hypospadias rates outside of Europe. Additional investigation of a possible increase in hypospadias rates is warranted.     

Urban/Rural Differences in Decision Making and the Use of Advance Directives Among Nursing Home Residents at Admission

CONTEXT: Advance directives promote patient autonomy and encourage greater awareness of final care options while reducing physician and family uncertainty regarding patient preferences. PURPOSE: To investigate differences in decision making authority and the use of advance directives among nursing home residents admitted from urban and rural areas. METHODS: A total of 551,208 admission assessments in the Minimum Data Set were analyzed for all residents admitted to a nursing facility in 2001. Using the Rural Urban Commuting Areas (RUCA) methodology and ZIP code of primary residence before admission, these residents were classified into 4 urban/rural areas. FINDINGS: Residents from rural areas were significantly more likely to have executed a durable power of attorney for health care or for financial decisions than residents admitted from the other areas, with the largest differences observed between residents admitted from urban and rural areas. Almost 6 residents in 10 from urban areas had no advance directives in place at admission compared with only 4 residents in 10 admitted from rural areas. CONCLUSIONS: Health providers and social workers in both rural and urban areas should advise patients about the value of advance directives.     

In vitro and in vivo antifungal activities of the eight steroid saponins from Tribulus terrestris L. with potent activity against fluconazole-resistant fungal pathogens

Antifungal activity of natural products is being studied widely. Saponins are known to be antifungal and antibacterial. We have isolated eight steroid saponins from Tribulus terrestris L. , namely TTS-8, TTS-9, TTS-10, TTS-11, TTS-12, TTS-13, TTS-14 and TTS-15. TTS-12 and TTS-15 were identified as tigogenin-3-O-β-D-xylopyranosyl（1→ 2）-[-β-D-xylopyranosyl（ 1 → 3 ） 3-β- D-glucopyranosyl （ 1 → 4 ）- 1- α-L-rhamnopyranosyl （ 1 → 2 ） 3-β-D-galactopyranoside and tigogenin-3-O-β-D-glucopyranpyranosyl（1→2）-[-β-D-xylopyranosyl（1→ 3）3-β-D-glucopyranosyl（1→4）-β-D-galactopyranoside, respectively. The in vitro antifungal activities of the eight saponins against six fluconazole-resistant yeasts, Candida albicans, Candida glabrata, Candida para psilosis , Candida tropicalis , Candida krusei , and Cryptococcus neo f ormans were studied using microbroth dilution assay. The results showed that TTS-12 and TTS-15 were very effective against several pathogenic candidal species and C. neoformans in vitro. It is noteworthy that TTS-12 and TTS-15 were very active against fluconazole-resistant C. albicans （MIC80 = 4.4, 9.4 mg/ml）, C. neoformans （MIC80 =10.7, 18.7 mg/ml） and inherently resistant C. krusei （MIC80 =8.8, 18.4 mg/ml）. So in vivo activity of TTS-12 in a vaginal infection model with fluconazole-resistant C. albicans was studied in particular. Our studies revealed TTS-12 also showed in vivo activities against fluconazole-resistant yeasts. In conclusion, steroid saponins TTS-12 and TTS-15 from Tribulus terrestris L. have significant in vitro antifungal activity against fluconazole-resistant fungi, especially TTS-12 also showed in vivo activity against fluconazole-resistant C. albicans.