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  • Professor of Medicine, Harvard Medical School, Chief, Brigham and Women's/Faulkner Cardiology, Brigham and Women's Hospital, Boston, Massachusetts


Because chemotherapy is administered very soon after biopsy and diagnosis prostate cancer 911 purchase 60 pills speman free shipping, treatment of the micrometastases known to mens health zucchini carbonara 60pills speman fast delivery be present in the majority of patients can be instituted early prostate volume normal discount speman 60pills online. This offers a substantial advantage over the traditional adjuvant approach prostate cancer images buy speman 60pills, in which the administration of systemic chemotherapy is delayed by 1 month or more for surgery and wound healing. Earlier administration of systemic treatment may reduce the emergence of drug-resistant cells in the micrometastases. Grading systems are necessarily imprecise and subject to sampling errors; however, with scrupulous attention to adequate sectioning from many sites of the surgical specimen, the degree of response can be reliably and reproducibly assessed. The grading system designed at Memorial Sloan-Kettering Cancer Center by Huvos and colleagues 98,188 has been used widely (Table 39. Thus, patients at high risk for recurrent disease can apparently be identified early in treatment on the basis of poor response to presurgical chemotherapy. The Huvos grading system has served as a model for other systems for grading tumor response. Histologic Grading of the Effect of Preoperative Chemotherapy on Primary Osteosarcoma Although the predictive value of tumor response to presurgical chemotherapy is now indisputable, a number of problems have surfaced in the application of such response grading to patient management. Different criteria for the definition of favorable and unfavorable response are used in different grading systems, making comparisons among studies difficult. Anderson Cancer Center divides response into three categories: (1) no effect or doubtful effect with less than 40% tumor destruction; (2) partial effect with 40% to 60% tumor destruction; and (3) definite effect, in which more than 60% of the tumor is destroyed and fibrovascular regeneration is present. Perhaps most problematic are the differences among studies conducted to date in the timing of surgery relative to the initiation of chemotherapy, and especially the variable duration of exposure to chemotherapy before definitive surgery and histologic evaluation of the response of the primary tumor. It appears that presurgical chemotherapy regimens of longer duration are associated with a higher proportion of "favorable" responders. An analysis from the Memorial Sloan-Kettering Cancer Center suggests that this is indeed the case. As noted above, results of studies from the Memorial Sloan-Kettering Cancer Center and elsewhere suggest that patients whose tumors are responsive to presurgical therapy are destined to do well when the same therapy is continued postoperatively. Patients whose tumors are unresponsive to the presurgical regimen have a much less favorable outlook and might benefit from a change in chemotherapeutic agents. This strategy was pioneered at Memorial Sloan-Kettering in the T-10 protocol 51,98 (see. Although only 39% of patients achieved a favorable histologic response to presurgical chemotherapy (51% if only patients younger than 21 years were analyzed), virtually all of the favorable responders were projected to survive free of recurrence. Overall, in preliminary reports, 90% of patients treated on the T-10 regimen with tailored therapy were projected to remain disease-free at 3 years. Moreover, a significant difference in outcome could no longer be detected between those who did and did not respond to presurgical chemotherapy, supporting the contention that poor responders were "salvaged" by the administration of alternative chemotherapy postoperatively. Because of these very favorable preliminary results, the T-10 protocol served as a model for many of the osteosarcoma treatment studies launched in the 1980s and 1990s, virtually all of which featured presurgical chemotherapy and tailoring of treatment on the basis of responsiveness of the primary tumor. Responses in the primary tumor have been variable, with favorable responses observed in 30% to 85% of patients. The overall results are excellent but are comparable to adjuvant studies that used regimens of equal intensity without any preoperative chemotherapy (see Table 39. Furthermore, the importance of custom tailoring of therapy in this strategy remains to be defined. The remaining poor-responding patients did not benefit from a change in therapy postoperatively and had a less favorable outcome (projected 5-year event-free survival, 49%). At the Rizzoli Institute, 177,201 overall results have improved over time, concurrent with the adoption of the strategy of presurgical chemotherapy. However, the Rizzoli investigators conclude that the improvement in prognosis more likely reflects increased effectiveness of the agents used rather than the use of presurgical chemotherapy per se, because a group of patients treated concurrently at the same institution without the benefits of presurgical chemotherapy fared just as well as patients treated with presurgical chemotherapy. Seventy-one percent of patients in this study achieved a favorable response to presurgical chemotherapy, and 71% of these patients were projected to be disease-free survivors at 5 years. Of note, the poorly responding patients had a projected disease-free survival equal to that of good responders if only patients receiving adequate therapy were considered.

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In patients with widespread disease prostate cancer 4 big questions generic 60pills speman otc, local therapy is often used to prostate cancer how long to live order speman 60pills line provide palliation for specific symptoms mens health 7 day workout purchase speman 60pills overnight delivery. At times prostate natural supplements generic 60 pills speman with amex, local therapy is administered in conjunction with systemic therapy, although one must be careful about the potential increase in toxicity that may be seen with the concurrent administration of chemotherapy and radiation. Decisions about the use of local therapy in the patient with advanced disease can be complex. Administration and Choice of Systemic Therapy the vast majority of patients with metastatic breast cancer receive some form of systemic therapy. Visceral disease, particularly low-volume and asymptomatic disease, is not a contraindication to the use of hormonal therapy; however, the patient with extensive visceral disease is probably better served by chemotherapy. In general, there is little evidence that one hormonal therapy is substantially more effective than another. As a result, the ease of administration and tolerability usually dictates the choice of treatment. Hormonal Therapy for Women with Metastatic Breast Cancer In premenopausal women who have never received hormonal therapy, tamoxifen is generally the treatment of choice. A small randomized trial has suggested that tamoxifen and ovarian ablation are equivalent in efficacy. European trials have evaluated the use of a combination of ovarian ablation and tamoxifen in patients with metastatic breast cancer. In some studies, there has been a suggestion of an improved overall response rate, 715,716 but it remains unclear if this approach is superior to sequential therapy. Aromatase inhibitors are not active in premenopausal women because of the high levels of circulating estrogen from the ovaries. Aromatase inhibitors can be used in conjunction with ovarian ablation, although there is little published information about this combination. In the metastatic setting, toremifene is an acceptable alternative based on the equivalence demonstrated between the two agents in randomized trials. A randomized trial demonstrated the equivalence of anastrozole (Arimidex) and tamoxifen in patients who had had no prior hormonal therapy, 720 making it reasonable to consider these agents as first-line therapy even in patients who have never received tamoxifen. Objective response rates to the aromatase inhibitors have been in the 10% to 20% range, but a substantial number of patients in these trials have had disease stabilization for 6 months or longer. In both premenopausal and postmenopausal women, occasional responses can be seen with withdrawal of either high-dose estrogen (now rarely used), tamoxifen, or progestins. Many patients treated with hormonal therapy have bone-only disease, making response assessment complex. In addition, it can take up to several months to see a response in some patients, whereas others have more rapid disease regressions. A flare phenomenon with worsening bone pain, increasing soft tissue lesions, hypercalcemia, or all three is seen in a small percentage of patients who are started on hormonal therapy. With either hormonal therapy or chemotherapy, there can be a rise in tumor marker levels, alkaline phosphatase, or both early in the course of therapy, with a subsequent decline. Clinicians should not continue hormonal therapy in patients with rapid or unequivocal evidence of disease progression. In the minimally symptomatic patient, it is often prudent to continue therapy for several months if there is an uncertainty concerning the response to treatment. In these situations, it is important to explain to patients that a change in therapy in the near future may be necessary, but that there is little to be lost by continuing the hormonal approach with close monitoring of disease status. A question that often arises is how many hormonal regimens to administer before moving on to chemotherapy. In a patient who has had a prior response to (or extended disease stabilization with) hormonal therapy, there is a reasonable chance of observing a response with another hormonal approach.

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The patient did not wish to prostate surgery recovery order speman 60pills free shipping have reconstructive surgery done on the helix of the ear mens health lunch box cheap speman 60pills otc. Basal cell cancer on the antihelix is not uncommon prostate cancer generic speman 60 pills free shipping, and the recommended treatment is Mohs micrographic excision androgen hormone gel cheap speman 60 pills visa. Retraction of surrounding tissue indicates deeply infiltrative nature of the cancer. The patient was treated with Mohs micrographic surgery and referred for reconstruction to minimize the risk of ectropion. Although basal cell carcinoma is most common in light-skinned people, it can occur in more darkly pigmented individuals. Extensive basal cell carcinoma of the left nose extending into the medial canthus and along the lower eyelid. Following Mohs micrographic surgery, the patient was referred for plastic reconstruction. Because of the large size of the lesion, the patient must be monitored for recurrence. The location in the medial canthus, the long-standing nature of the cancer, and its size create a high risk that if the lesion recurs it will extend into the orbit. This clinical appearance suggests that the cancer likely extends deeply and may be at risk for involving the infraorbital nerve. Basal cell cancer in this region can extend widely along the cartilage and posterior scalp before it is diagnosed. Nodular basal cell carcinoma within an area of previous excision consistent with recurrent cancer. Because of the extensive nature of this cancer, radiation therapy was used with a good result. Multiple nodular and papular lesions on the scalp in an individual with severe solar damage. Although the clinical diagnosis of the large lesion on the right is basal cell cancer, the red nodular lesions are concerning and require biopsy as well to obtain a definitive diagnosis. This was successfully treated with radiation therapy, although Mohs micrographic surgery and reconstruction would have been an equally acceptable alternative. This highlights the likely association between solar exposure, secondary to clothing styles, and basal cell cancer. Additional basal cell cancer on the lower extremity in the same patient as in. Multiple basal cell carcinomas of the lower extremity with evidence of venous stasis changes. Treatment of cancer in this area is extremely difficult because of the dependent location and the resultant slow healing in older patients. Treatment by Mohs micrographic excision with healing by second intention provides excellent results. While skin grafting creates secondary wounds in the patient that require additional healing, new biologic dressings and allograft permit excellent healing while minimizing limitations on activity. Nodular basal cell carcinoma on the upper extremity, side view, indicating the exophytic nature. A: Basal cell carcinoma with ill-defined clinical margins on the nasal tip of a 50-year-old man. Biopsy confirmed the presence of rosacea but also revealed a few foci of superficial basal cell carcinoma. Basal cell carcinoma on the philtrum complicated by an outbreak of herpes labialis. This case highlights the occasional misdiagnosis of basal cell carcinoma for herpes labialis. The chronic, recurring nature of both, in certain circumstances, may be responsible for the confusion. Biopsy was eventually performed when the patient was seen by his dermatologist, and it revealed basal cell cancer. E: Recurrent basal cell carcinoma at upper edge of graft 10 years after original surgery. Surgery and radiation therapy are generally the only treatments currently available. Photodynamic therapy, incorporating the use of topical aminolevulinic acid, which avoids systemic adverse effects, holds promise for treatment of large numbers of lesions.

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The cardiac disease is due to prostate knot buy speman 60 pills with amex fibrosis involving the endocardium androgen hormone 2 ep7 purchase speman 60 pills visa, primarily of the right side of the heart prostate x supplement cheap speman 60 pills online, although left side lesions can also occur mens health events buy 60 pills speman with mastercard. These fibrous deposits tend to cause constriction of both the tricuspid and pulmonic valves. At the pulmonic valve, stenosis is usually predominant, whereas at the tricuspid valve, the constriction results in the valve being fixed open, and tricuspid regurgitation is usually predominant. Its occurrence and severity are directly related to tumor size in an area that drains into the systemic circulation. Because midgut tumors are the most common and frequently metastasize, midgut tumors account for 60% to 87% of the carcinoid syndrome, foregut tumors for 2% to 33%, hindgut for 1% to 8%, and an unknown primary location for 2% to 15% (see Table 38. When 44 consecutive cases were studied before any resection, 84% of the patients had serotonin overproduction. Platelet serotonin was elevated in 96%, 43%, and 0% of patients with midgut, foregut, and hindgut carcinoids, respectively. Urinary dopamine and catecholamine metabolites were elevated in 38% and 33% of midgut, 20% and 20% of foregut, and 7% and 14% of hindgut carcinoids, respectively. In a large review 12 of 748 cases of carcinoid syndrome, 92% had increased serotonin activity. Arrows indicate the sites of action of therapeutic agents used in the treatment of carcinoid syndrome. Patients may develop either a typical or atypical type of carcinoid syndrome (see. The exact etiology of the flushing in patients with carcinoid syndrome may differ depending on the different tumor types. In patients with gastric carcinoids, the red, patchy, pruritic flush is thought to be caused by histamine, 82 because this type of flushing can be prevented by the use of H 1- and H2-receptor antagonists. In one study, 99 octreotide relieved pentagastrin-induced flushing in all patients without necessarily altering the substance P response. Furthermore, pentagastrin caused flushing in some patients without rises in plasma substance P, suggesting that mediators other than substance P must be important in inducing the flushing. Patients with carcinoid syndrome had decreased absorption of sodium, potassium, chloride, and water in the jejunum and increased intraluminal nonsubstance P tachykinin and prostaglandin E 2 concentrations compared with normal controls. False-positives may occur if the patient is eating serotonin-rich foods, such as bananas, plantains, pineapple, kiwi fruit, walnuts, hickory nuts, pecans, and avocados, which falsely elevate urinary levels. However, urinary and platelet measurement of serotonin itself may give additional information; thus, it has been recommended that these should also be measured. In 14 foregut carcinoids, the sensitivities were 50%, 29%, and 55%, respectively; for 25 midgut carcinoids, the sensitivities were 100%, 92%, and 82%, respectively; and for hindgut carcinoids, the sensitivities were 20%, 0%, and 60%, respectively. The data demonstrate the increased sensitivity of measuring platelet serotonin levels. The diagnosis of a carcinoid may be suspected by clinical symptoms suggestive of carcinoid syndrome or by the presence of the other clinical symptoms, such as abdominal pain or diarrhea, or it can be made in relatively asymptomatic patients from the pathology report at surgery or after liver biopsy for hepatomegaly. Ileal carcinoids, which make up more than 25% of all clinically detected carcinoids, should be suspected if a patient presents with bowel obstruction, abdominal pain, flushing, or diarrhea. In patients with symptomatic tumors, the time from onset of symptoms until diagnosis is frequently delayed, varying from 1 to 2 years. A number of studies 122,123 and 124 demonstrate that serum chromogranin A levels are elevated in 56% to 100% of patients with carcinoids, and the level correlates with tumor bulk. Five subtypes (numbered sst1 to sst5) of somatostatin receptors have been described. More recent studies demonstrate that it has a higher specificity than bone scanning and equal or greater sensitivity. The percentage of carcinoids in different locations having localized disease, regional metastases, or distant metastases varies widely. The highest percentage of nonlocalized disease is with pancreatic (91%), colonic (77%), and small intestinal carcinoids (75%), whereas the highest percentage with localized disease is the larynx (100%), followed by the ovary, appendix, and rectum (62% to 95%).

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