Platelet activation status decreases after menopause

Objective.?The aim of the study was to investigate the impact of the climacterium (before and after menopause) on platelet activation.

Background.?Platelet activation has been associated to the risk of cardiovascular disease. There is much speculation about the relationship between platelet function and sex steroids, due to peculiarities of platelet action between the genders, including concerns about the influence of low estradiol status in menopausal women.

Methods.?By means of a cross-sectional study design, 37 female patients divided into two groups were compared. Group A consisted of ten women, mean age 43.9 years, in the premenopausal period, with normal estrogen levels; and Group B comprised 27 patients, mean age 53.0 years, who had all reached menopause. Platelet activation markers, namely P-selectin and glycoprotein IIb–IIIa complex (GPIIb–IIIa), were evaluated by flow cytometry with monoclonal antibodies. A binding index was calculated for both parameters (percentage of positive platelets?×?mean fluorescence of positive platelets). Also, thromboxane A₂ was quantified by means of its main plasma metabolite, thromboxane B₂, by enzyme immunoassay.

Results.?P-selectin and GPIIb–IIIa expression results revealed lower platelet activation status after menopause, as there was a decrease in both the percentage of P-selectin^?+? platelets and of GPIIb–IIIa mean fluorescence of positive platelets, lowering both binding indices. P-selectin binding index differed significantly between Group A (12.3?±?3, n?=?10) and Group B (6.2?±?2.9, n?=?27; mean?±?standard deviation (SD), p?<?0.001). GPIIb–IIIa binding index also differed significantly between both groups (Group A: 18.8?±?2.3, n?=?10 vs. Group B: 16.2?±?3.1, n?=?27; mean?±?SD, p?<?0.0018). Plasma concentration of thromboxane B₂ was 1.07?±?0.5?pg/well before menopause (Group A, n?=?10) and 1.9?±?4.1?pg/well after menopause (Group B, n?=?27), not significantly different (mean?±?SD, baseline?×?therapy, p?=?0.85).

Conclusions.?After the menopause, climacteric women – whose estradiol status is low – have a decreased activation platelet status compared with premenopausal women. Nevertheless, further studies on a larger sample are necessary for conclusive data regarding cardiovascular disease.     

Responses to superficial heating and cooling differ in men and women with knee osteoarthritis

This investigation assessed differences between the response of men and women with knee osteoarthritis to superficial heat, cold, or contrast therapy applied with a water-circulating system or a standard heating pad, and rest. We further analyzed data from a previous study to better understand the influence of gender on the response to treatment based on Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales and a visual analog pain scale (VAS). Using a within-subject, randomized order design, 34 patients received each treatment in 1-week blocks. A KOOS questionnaire and VAS were completed at baseline and twice each week. Women were more likely to report clinically meaningful improvement in pain and symptoms on the KOOS with the use of heat, cold, and a heating pad. There were no significant differences in response to treatment between men and women for the function-daily living and quality of life subscales or percent pain reduction on the VAS. Men and women reported improved quality of life with intervention. Women are more likely to report clinically meaningful improvement in pain and symptoms associated with knee OA following the use of superficial heat, cold, or a heating pad than men.     

Decreasing accidental mortality of ventilator-dependent children at home: a call to action

An estimated 8,000 children in the United States are dependent on mechanical ventilation at home. Despite technological advances for home monitoring of ventilated patients, the preventable death rate among these children has not changed significantly during the last 2 decades. Analysis of the data indicate that the primary causes of preventable death in ventilator-dependent children at home are inadequate training, improper response, and a lack of vigilance by the clinicians who care for them.     

alpha6 Integrin Cleavage: Sensitizing human prostate cancer to ionizing radiation

Purpose: The goal was to determine if prostate tumor cells containing a mutant α6 integrin would be defective in tumor re-population following clinically relevant fractionated ionizing radiation (IR) treatments.

Material and methods: Human prostate cancer cells derived from PC3N cells were used which conditionally expressed a cleavable, wild type form of α6 integrin (PC3N-α6-WT) or a mutated non-cleavable form of α6 integrin (PC3N-α6-RR). The resulting tumor growth before, during and after fractionated doses of IR (3 Gy×10 days) was analyzed using the endpoints of tumor growth inhibition (T/C), tumor growth delay (T-C), tumor doubling time (Td) and tumor cell kill (Log₁₀ cell kill).

Results: The T/C values were 36.1% and 39.5%, the T-C values were 20.5 days and 28.5 days and the Td values were 5.5 and 10.5 days for the irradiated PC3N-α6-WT and PC3N-α6-RR cells, respectively. The Log₁₀ was 1.1 for the PC3N-α6-WT cells and 0.8 for the PC3N-α6-RR cells. The tumor response to IR was altered in tumors expressing the mutant α6 integrin as indicated by a significant increase in tumor growth inhibition, an increase in tumor growth delay, an increase in tumor doubling time and an increase in tumor cell kill.

Conclusions: Blocking integrin cleavage in vivo may be efficacious for increasing the IR responsiveness of slow growing, pro-metastatic human prostate cancer.     

Subclinical pretreatment sensory deficits appear to predict the development of pain and numbness in patients with multiple myeloma undergoing chemotherapy

Purpose

Chemotherapy-induced peripheral neuropathy is a major complication in the treatment for cancer, including multiple myeloma (MM). Patients may develop painful and non-painful (e.g., numbness) neuropathy symptoms that impair function and often persist after therapy is terminated. This study tested the hypothesis that baseline subclinical neuropathy, as assessed by sensory thresholds, is related to the development of neuropathy symptoms (e.g., pain and numbness) in patients with MM undergoing treatment with chemotherapy.

Methods

Patients (n = 56) who had undergone two or fewer cycles of induction therapy and who had no evident neuropathy were assessed using quantitative sensory tests to determine multiple-modality sensory thresholds. Patient-reported pain and numbness were assessed through induction therapy (16 weeks) via the MD Anderson Symptom Inventory. A subset of participants (n = 15) continued reporting on their symptoms for an additional 16 weeks (“maintenance phase”).

Results

Patients with sharpness detection deficits at baseline (n = 11, 20 % of sample) reported less severe pain and numbness during induction therapy and less numbness during maintenance therapy (P < 0.05). During the maintenance phase, patients with warmth detection deficits (n = 5, 38 % of sample) reported more severe pain and numbness, and those with skin temperature deficits (n = 7, 47 % of maintenance sample) reported more severe pain (P < 0.05). These deficits were related to patient reported difficulty walking, a common symptom of peripheral neuropathy.

Conclusion

Our results suggest that baseline subclinical sensory deficits may be related to a patient’s risk for developing chemotherapy-induced peripheral neuropathy.     

Inactivation of the vitamin D receptor in APC(min/+) mice reveals a critical role for the vitamin D receptor in intestinal tumor growth

Emerging evidence supports an inhibitory role for vitamin D in colorectal carcinogenesis; however, the mechanism remains unclear. The adenomatous polyposis coli (APC)/β-catenin pathway plays a critical role in colorectal carcinogenesis. The purpose of our study is to explore the interactions of vitamin D and APC/β-catenin pathways in intestinal tumor development. APC(min/+) mice with genetic inactivation of the vitamin D receptor (VDR) were generated through breeding. Intestinal tumorigenesis was compared between APC(min/+) and APC(min/+) VDR(-/-) mice at different ages. No differences were seen in the number of small intestinal and colonic tumors between APC(min/+) and APC(min/+) VDR(-/-) mice aged 3, 4, 6 and 7 months. The size of the tumors, however, was significantly increased in APC(min/+) VDR(-/-) mice in all age groups. Immunostaining showed significant increases in β-catenin, cyclin D1, phosphorylated Stat-3 and MSH-2 levels and decreases in Stat-1 in APC(min/+) VDR(-/-) tumors compared to APC(min/+) tumors. These observations suggest that VDR signaling inhibits tumor growth rather than tumor initiation in the intestine. Thus, the increased tumor burden in APC(min/+) VDR(-/-) mice is likely due to the loss of the growth-inhibiting effect of VDR. This study provides strong evidence for the in vivo relevance of the interaction demonstrated in vitro between the vitamin D and β-catenin signaling pathways in intestinal tumorigenesis.     

Photofrin photodynamic therapy for treatment of AIDS-related cutaneous Kaposi's sarcoma.

OBJECTIVE: Kaposi's sarcoma, the most common malignancy in AIDS patients, often presents with painful cutaneous lesions that are difficult to treat effectively despite a wide variety of therapeutic approaches. We used photodynamic therapy in an attempt to provide effective palliative treatment for this disease. METHODS: Photodynamic therapy utilizes the activation by light of a photosensitizing drug that preferentially accumulates in tumor tissue such as Kaposi's sarcoma. We enrolled 25 patients who received 1.0 mg/kg of Photofrin 48 h before exposure to 100-400 J/cm2 of 630 nm light. RESULTS: Of the 348 lesions treated, 289 were evaluable: 32.5% had complete clinical response, 63.3% had partial clinical response and 4.2% were clinical failures. There was a strong correlation between response and light dose: 54% of lesions achieved a complete clinical response at optimum light dose (> 250 J/cm2). There was no correlation of response with CD4 cell count nor was there a change in CD4 cell count post-treatment. At 400 J/cm2 full field scabbing and necrosis occurred in 90% of the treated fields. Thus, the maximum tolerated dose was determined to be 300 J/cm2. At light doses of 250 J/cm2 and below the toxicities were limited to erythema and edema in the treatment field. Forty-three biopsies were taken 0.5 h to 4 months post-treatment. These showed little change in the B and T cell infiltrates identified. Kaposi's sarcoma cells disappeared post-treatment in certain lesions. CONCLUSION: Photofrin is effective palliative treatment for HIV-associated Kaposi's sarcoma.