Randomized comparison of tamoxifen versus diethylstilbestrol in estrogen receptor-positive or -unknown metastatic breast cancer: a Southeastern Cancer Study Group trial

In a randomized study 115 postmenopausal women with advanced breast cancer who were estrogen receptor-unknown or -positive were treated initially with tamoxifen or diethylstilbestrol (DES). Their pretreatment characteristics showed no significant difference. The frequency of response was identical with tamoxifen and DES, showing a complete response rate of 2% versus 2% and a partial response rate of 4% versus 8%, respectively; stable disease was present in 78% versus 73% of the patients, respectively. The median time to disease progression (5 vs 6 months) and median survival depending on initial hormone therapy (34 vs 35 months) were identical for tamoxifen and DES, respectively. Gastrointestinal toxicity was more frequent and more severe with DES than tamoxifen. Responses were seen with withdrawal of each agent and on crossover to the alternative agent. Our conclusions are that: DES and tamoxifen are equally effective in treating metastatic breast cancer in the postmenopausal patient who is estrogen receptor-positive or -unknown; withdrawal and crossover responses are seen with both agents; side effects are minimal but more frequent with DES; and on the basis of cost-effectiveness DES is the preferable agent.     

In vitro clonal propagation of Achyranthes aspera L. and Achyranthes bidentata Blume using nodal explants

Objective

To develop the reproducible in vitro propagation protocols for the medicinally important plants viz., Achyranthes aspera (A. aspera) L. and Achyranthes bidentata (A. bidentata) Blume using nodal segments as explants.

Methods

Young shoots of A. aspera and A. bidentata were harvested and washed with running tap water and treated with 0.1% bavistin and rinsed twice with distilled water. Then the explants were surface sterilized with 0.1% (w/v) HgCl₂ solutions for 1 min. After rinsing with sterile distilled water for 3–4 times, nodal segments were cut into smaller segments (1 cm) and used as the explants. The explants were placed horizontally as well as vertically on solid basal Murashige and Skoog (MS) medium supplemented with 3% sucrose, 0.6% (w/v) agar (Hi-Media, Mumbai) and different concentration and combination of 6-benzyl amino purine (BAP), kinetin (Kin), naphthalene acetic acid (NAA) and indole acetic acid (IAA) for direct regeneration.

Results

Adventitious proliferation was obtained from A. aspera and A. bidentata nodal segments inoculated on MS basal medium with 3% sucrose and augmented with BAP and Kin with varied frequency. MS medium augmented with 3.0 mg/L of BAP showed the highest percentage (93.60±0.71) of shootlets formation for A. aspera and (94.70±0.53) percentages for A. bidentata. Maximum number of shoots/explants (10.60±0.36) for A. aspera and (9.50±0.56) for A. bidentata was observed in MS medium fortified with 5.0 mg/L of BAP. For A. aspera, maximum mean length (5.50±0.34) of shootlets was obtained in MS medium augmented with 3.0 mg/L of Kin and for A. bidentata (5.40±0.61) was observed in the very same concentration. The highest percentage, maximum number of rootlets/shootlet and mean length of rootlets were observed in 1/2 MS medium supplemented with 1.0 mg/L of IBA. Seventy percentages of plants were successfully established in polycups. Sixty eight percentages of plants were well established in the green house condition. Sixty five percentages of plants were established in the field.

Conclusions

The results have shown that use of nodal buds is an alternative reproducible and dependable method for clonal propagation of A. aspera and A. bidentata. The high rate of direct shoot-root multiplication and their high rate of post-hardening survival indicate that this protocol can be easily adopted for commercial large scale cultivation.     

Five-year retrograde transpopliteal angioplasty results compared with antegrade angioplasty

INTRODUCTION

Retrograde transpopliteal angioplasty (PA) is a potentially useful alternative technique for endovascular treatment of infra-inguinal arterial disease when antegrade transfemoral puncture (FA) is technically not possible or appropriate. This study aimed to investigate the outcomes of PA compared with FA during a 5-year period.

PATIENTS AND METHODS

A retrospective study was performed to assess 88 PA and 275 FA performed between January 2003 and January 2008. Assessments of patients, indication for procedure, disease site, stenosis severity, procedure outcomes and time to further intervention were recorded.

RESULTS

FA was used to treat more patients with critical ischaemia (42.2% vs 30.7%; P = 0.014)). PA was used to treat more proximal superficial femoral lesions (P < 0.001) and occlusive lesions (P = 0.001). Overall, 84.1% of PA and 82.5 % of FA were technically successful. There was no difference in local puncture site complication rates. Significantly more FA resulted in distal thrombus/embolism (8.4% vs 3.4%; P = 0.044). Further intervention was required in 27.3% of PA and 36.0% of FA. The time interval to re-intervention was not different between the groups.

CONCLUSIONS

PA is safe with comparable success rates and long-term outcomes to an FA. PA is a useful alternative approach or treating occlusive, proximal disease.     

Correlation of CD4+ T cell count with total lymphocyte count, haemoglobin and erythrocyte sedimentation rate levels in human immunodeficiency virus type-1 disease

Background: Studies in human immunodeficiency virus (HIV) infected adults have demonstrated association of total lymphocyte count (TLC) <1200/mm³ and subseqnent disease progression or mortality. The association of other surrogate makers such as haemoglobin (Hb), and erythrocyte sedimentation rate (ESR) with CD4 count and disease progression has also been suggested. This study was carried out to determine the relationship of CD4-positive T lymphocyte counts with TLC, Hb and ESR in HIV-infected individuals.Methods: The study population comprised of 215 antiretroviral treatment naive HIV-1 infected adults. The CD4 positive T cell counts, TLC, Hb and ESR of study participants were measured. Spearman's rank order correlation and Receiver Operating Characteristic were used for statistical analyses.Result: The sensitivity, specificity, positive and negative likelihood ratios for cut-off value of TLC <1200/mm³ for predicting CD4 counts <200 cells/mm³ and <350 cells/mm³ were 9.4%, 100%, not measurable and 1.1, and 6.1 %, 98.8 %, 5.13 and 0.95, respectively. The association of Hb (<10, 11, 12 g/dl and <10, 12, 14 g/dl for CD4 counts <200 cells/mm³ and <350 cells/mm³, respectively), and ESR (<10, 20 and 30 mm fall after 1 hour) with these two CD4 counts cut-off values were suboptimal.Conclusion: This study reveals the poor association of TLC, Hb, and ESR with CD4 counts in HIV infected adults, thus highlighting the need to review the utility of these surrogate markers, for predicting CD4 counts in people living with HIV/AIDS.     

Psychosocial impact of Von Hippel–Lindau disease: levels and sources of distress

Lammens CRM, Bleiker EMA, Verhoef S, Hes FJ, Ausems MGEM, Majoor‐Krakauer D, Sijmons RH, Luijt van der RB, Ouweland van den AMW, Van Os Tam, Hoogerbrugge N, Gomez‐Garcia EB, Dommering CJ, Gundy CM, Aaronson NK. Psychosocial impact of von Hippel–Lindau disease: levels and sources of distress. Von Hippel–Lindau disease (VHL) is a hereditary tumor susceptibility syndrome, characterized by an increased risk of developing multiple benign and malignant tumors at various sites and ages with limited preventive options. This study evaluates the prevalence of distress among VHL family members and factors associated significantly with such distress. Forty‐eight families with a VHL mutation were identified via the nine family cancer clinics in the Netherlands. In total, 171 family members (carriers, 50% at‐risk, non‐carriers) were approached, of whom 123 (72%) completed a self‐report questionnaire. Approximately 40% of the VHL family members reported clinically relevant levels of distress, approaching 50% among the carriers and, possibly even more striking, 36% among the non‐carriers. Having lost a first degree relative due to VHL during adolescence (OR 11.2; 95% CI 1.4–86.9) was related significantly to heightened levels of distress. Approximately, only one‐third of those who reported heightened levels of distress had received professional psychosocial support. A substantial percentage of family members experience clinically relevant levels of distress. We would recommend the introduction of a procedure for screening for distress in this vulnerable population. Special attention should be paid to those individuals who have lost a close relative due to VHL during adolescence.     

Effects of intravenous and subcutaneous administration on the pharmacokinetics, biodistribution, cellular uptake and immunostimulatory activity of CpG ODN encapsulated in liposomal nanoparticles

We have previously demonstrated that the immune response to an unmethylated cytidine-guanosine (CpG)-containing oligonucleotide (ODN) is greatly enhanced when encapsulated in a lipid nanoparticle (LN-CpG ODN). In this study, the pharmacokinetics, biodistribution and cellular uptake of LN-CpG ODN following intravenous (i.v.) and subcutaneous (s.c.) administration was characterized and correlated with immunostimulatory activity. It is shown that, despite dramatic differences in tissue distribution profiles and considerable differences in uptake by CD11c-positive, CD11b-positive, Mac-3-positive and CD45R/B220-positive cells following i.v. and s.c. administration, the resultant immune response is very similar with respect to levels of cellular activation (DX5, Mac-3, CD11b, CD45/B220, CD4, CD8 and CD11c) and cytolytic activity of immune cells [natural killer (NK) cells and monocytes/macrophages] in the spleen and blood compartments. Some differences in response kinetics and antibody-dependent cellular cytotoxicity (ADCC) activity were noted in the peripheral blood NK cell population. Analyses of particle biodistribution and cell types involved in uptake leads to the conclusion that the inherent ability of antigen-presenting cells (APCs) to sequester LN-CpG ODN results in efficient uptake of the particle, even when present at very low concentrations, leading to similar responses following i.v. and s.c. administration. These results contrast with the behavior of free CpG ODN, for which distinctly different immune responses are observed following i.v. or s.c. administration.     

Immunizations and pregnancy: An update for pharmacists

ObjectiveTo review the safety of immunizations in pregnancy.Data sourcesPubMed search using the termsvaccine, immunizations, andpregnancy, as well as current national guidelines.Data synthesisImmunizations for women of childbearing age are an integral component of pregnancy planning. Some vaccines are compatible with pregnancy, whereas others, in particular live-attenuated vaccines, are contraindicated because of the theoretical risk to the fetus. The immunizing pharmacist must be aware of updated guidelines regarding the safe and appropriate use of vaccines during pregnancy. Certain routine adult vaccines are contraindicated during pregnancy, including the live-attenuated intranasal influenza, measles–mumps–rubella, varicella, zoster, and human papillomavirus vaccines. The trivalent inactivated influenza vaccine is specifically recommended for all women who are pregnant during influenza season. The hepatitis B, tetanus–diphtheria–acellular pertussis, and several other routine adult and travel vaccines may be administered safely in pregnancy if the patient meets certain risk criteria. Breast-feeding is compatible with all routine adult vaccines. Vaccinia (smallpox) and yellow fever vaccines are cautioned against use except in certain circumstances.ConclusionPharmacists can play an important role in recommending safe and appropriate vaccines before and during pregnancy.     

Trevor's disease: the clinical manifestations and treatment of dysplasia epiphysealis hemimelica

Trevor's disease is a rare abnormality characterized by aberrant osteocartilaginous growth from an epiphysis. We describe six new cases from our institution. A patient with isolated tibial tuberosity involvement is described for the first time. Each patient was classified according to Azouz into localized (three), classical (two) and generalized (one) form. We recommend that parents be counseled regarding the progressive nature of this disorder owing to the chance of worsening deformity with surgical excision alone, and the need to be followed until skeletal maturity.