Side Effects Of Systemic Treatment Research Articles

Advances in polymer-based cell encapsulation and its applications in tissue repair.

Cell microencapsulation is a more widely accepted area of biological encapsulation. In most cases, it involves fixing cells in polymer scaffolds or semi-permeable hydrogel capsules, providing the environment for protecting cells, allowing the exchange of nutrients and oxygen, and protecting cells against the attack of the host immune system by preventing the entry of antibodies and cytotoxic immune cells. Hydrogel encapsulation provides a three-dimensional (3D) environment similar to that experienced in vivo, so it can maintain normal cellular functions to produce tissues similar to those in vivo. Embedded cells can be genetically modified to release specific therapeutic products directly at the target site, thereby eliminating the side effects of systemic treatments. Cellular microcarriers need to meet many extremely high standards regarding their biocompatibility, cytocompatibility, immunoseparation capacity, transport, mechanical, and chemical properties. In this article, we discuss the biopolymer gels used in tissue engineering applications and the brief introduction of cell encapsulation for therapeutic protein production. Also, we review polymer biomaterials and methods for preparing cell microcarriers for biomedical applications. At the same time, in order to improve the application performance of cell microcarriers in vivo, we also summarize the main limitations and improvement strategies of cell encapsulation. Finally, the main applications of polymer cell microcarriers in regenerative medicine are summarized.

Evolution, current challenges, and future possibilities in the objective assessment of aesthetic outcome of breast cancer locoregional treatment

The Breast Cancer overall survival rate has raised impressively in the last 20 years mainly due to improved screening and effectiveness of treatments. This increase in survival paralleled the awareness over the long-lasting impact of the side effects of treatments on patient quality of life, emphasizing the motto “a longer but better life for breast cancer patients”. In breast cancer more strikingly than in other cancers, besides the side effects of systemic treatments, there is the visible impact of surgery and radiotherapy on patients’ body image. This has sparked interest on the development of tools for the aesthetic evaluation of Breast Cancer locoregional treatments, which evolved from manual, subjective approaches to computerized, automated solutions. However, although studied for almost four decades, past solutions were not mature enough to become a standard.Recent advancements in machine learning have inspired trends toward deep-learning-based medical image analysis, also bringing new promises to the field of aesthetic assessment of locoregional treatments. In this paper, a review and discussion of the previous state-of-the-art methods in the field is conducted and the extracted knowledge is used to understand the evolution and current challenges. The aim of this paper is to delve into the current opportunities as well as motivate and guide future research in the aesthetic assessment of Breast Cancer locoregional treatments.

Nanoparticle-Mediated Remodeling of the Tumor Microenvironment to Enhance Immunotherapy.

Nanoscience has long been lauded as a method through which tumor-associated barriers could be overcome. As successful as cancer immunotherapy has been, limitations associated with the tumor microenvironment or side effects of systemic treatment have become more apparent. In this Review, we seek to lay out the therapeutic challenges associated with the tumor microenvironment and the ways in which nanoscience is being applied to remodel the tumor microenvironment and increase the susceptibility of many cancer types to immunotherapy. We detail the nanomedicines on the cutting edge of cancer immunotherapy and how their interactions with the tumor microenvironment make them more effective than systemically administered immunotherapies.

Locoregional therapies in cholangiocarcinoma.

Cholangiocarcinoma is a rare and aggressive malignancy of the biliary tract. Complete surgical resection can be curative, but the majority of patients are diagnosed with advanced disease and usually die within a year of diagnosis. Most deaths are attributable to local disease progression rather than distant metastases, supporting the use of locoregional therapies. There is evidence that locoregional therapies can provide local tumor control resulting in increased survival while avoiding some of the side effects of systemic treatments, increasing potential treatment options for patients who may be unsuitable for systemic palliative treatments. This review considers the evidence for locoregional therapies in cholangiocarcinoma, which can be classified into endoscopic, vascular, percutaneous and radiation oncological therapies. Current guidelines do not recommend the routine use of locoregional therapies due to a lack of prospective data, but the results of ongoing trials are likely to increase the evidence base and impact on clinical practice.

Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017

BackgroundIn advanced prostate cancer (APC), successful drug development as well as advances in imaging and molecular characterisation have resulted in multiple areas where there is lack of evidence or low level of evidence. The Advanced Prostate Cancer Consensus Conference (APCCC) 2017 addressed some of these topics. ObjectiveTo present the report of APCCC 2017. Design, setting, and participantsTen important areas of controversy in APC management were identified: high-risk localised and locally advanced prostate cancer; “oligometastatic” prostate cancer; castration-naïve and castration-resistant prostate cancer; the role of imaging in APC; osteoclast-targeted therapy; molecular characterisation of blood and tissue; genetic counselling/testing; side effects of systemic treatment(s); global access to prostate cancer drugs. A panel of 60 international prostate cancer experts developed the program and the consensus questions. Outcome measurements and statistical analysisThe panel voted publicly but anonymously on 150 predefined questions, which have been developed following a modified Delphi process. Results and limitationsVoting is based on panellist opinion, and thus is not based on a standard literature review or meta-analysis. The outcomes of the voting had varying degrees of support, as reflected in the wording of this article, as well as in the detailed voting results recorded in Supplementary data. ConclusionsThe presented expert voting results can be used for support in areas of management of men with APC where there is no high-level evidence, but individualised treatment decisions should as always be based on all of the data available, including disease extent and location, prior therapies regardless of type, host factors including comorbidities, as well as patient preferences, current and emerging evidence, and logistical and economic constraints. Inclusion of men with APC in clinical trials should be strongly encouraged. Importantly, APCCC 2017 again identified important areas in need of trials specifically designed to address them. Patient summaryThe second Advanced Prostate Cancer Consensus Conference APCCC 2017 did provide a forum for discussion and debates on current treatment options for men with advanced prostate cancer. The aim of the conference is to bring the expertise of world experts to care givers around the world who see less patients with prostate cancer. The conference concluded with a discussion and voting of the expert panel on predefined consensus questions, targeting areas of primary clinical relevance. The results of these expert opinion votes are embedded in the clinical context of current treatment of men with advanced prostate cancer and provide a practical guide to clinicians to assist in the discussions with men with prostate cancer as part of a shared and multidisciplinary decision-making process.

Promote Recurrent Aphthous Ulcer Healing with Low Dose Prednisolone Bilayer Mucoadhesive Buccal Film.

Recurrent aphthous ulcer (RAU) is one of the most common ulcerative diseases of the oral mucosa which is recurrent, painful and slow to heal. Treatment is primarily for pain relief and promotion of healing to shorten the disease duration or reduce the rate of recurrence. Development of a new design of topical buccal bilayer mucoadhesive films containing sodium alginate and gellan gum loaded with low dose of 1 mg prednisolone sodium phosphate to reduce the treatment period and decrease side effects of systemic treatment. Films were prepared by solvent casting technique and evaluated to ensure optimum film characteristics, and in vivo efficiency. The bilayer films were thin, flexible with good water uptake, mucoadhesive and mechanical properties. In vitro drug release was sustained and showed anomalous non-Fickian kinetics. SEM confirmed the development of bilayer formation. Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetery indicated no chemical interaction between the layers. In vivo study in rabbits with induced oral ulceration showed complete ulcer healing within 4-5 days by once daily treatment of the studied film. Histological examination indicated no inflammation on treatment sites compared to inflamed tissue on the control sites. The results suggested that buccal application of the developed bilayer mucoadhesive films loaded with only 1mg of prednisolone provided mucoadhesive and convenient application and was able to promote RAU healing with shorter treatment duration.

Abstract P5-15-08: Exercise intervention to run away from breast cancer treatment side effects: An integrative approach

Abstract Background. Some studies have shown that exercise increases breast cancer (BC) patients’ quality of life (QoL) during and after treatments. The aim of this study was to investigate the effect of an specific exercise intervention in QoL and in the exercise levels of these patients. Methods. A randomized controlled trial evaluated an intervention (IG) vs a control group (CG) in early stage BC patients who recently finished chemo & radio therapies. Intervention consists on controlled group classes combining aerobic and resistance activities. CG maintained their previous lifestyle. QoL, leisure-time exercise levels (LTEL), chest (CMS) and legs maximal strength (LMS), physical capacity (PC) and some psychological variables, were assessed at baseline and after 3 months in both groups. Women who participated in the IG were followed up (FU) after 6 months. Statistical analysis (SA) were performed using unpaired t-test on continuous variables comparing CG vs IG, considering possible confounders. Pearson correlation analyses were employed to examine possible correlations. 6 months FU data were analyzed comparing baseline and after intervention results using non-parametric test (n=13). SA was performed with SPSS v18 software. 95% CI was calculated and statistical significance level of p < 0.05 was used. Results. 59 women (median 48.97±8.35 years old) completed this study. No differences between groups were observed at baseline. Average attendance rate to the program was 89%. There was a significant rise in LTEL (t123=16.33; p=0.0001) and in QoL (t123=2.88; p=0.005) comparing IG vs CG. Results also showed a correlation between QoL and LTEL in patients of IG only (r=0.22; p=0.013). Significant differences between groups were observed in both physical and psychological variablesafter training program. Table 1. Results summary comparing intervention and control group.VARIABLESIntervention Group (n= 27) Mean±SDControl Group (n=32) Mean±SDFollow-Up (n=13) Mean±SDQoL*+112.88±17.74±103.11±19.26110.96±14.40LTEL*+45.11±14.6114.87±4.7834.56±19.51Body Fat Mass34.63±6.736.47±7.4735.74±4.56Muscle mass41.3±3.1638.78±8.5141.48±2.01Strength Index*+2.6±0.832.12±0.692.32±0.58CMS*+45.89±11.0731.47±9.8753.76±12.42LMS*+93.07±27.369.00±24.94114.65±24.29PC*+32.58±4.9627.08±3.7332.11±7.10FACT-F *+135.94±18.20124.00±24.20138.24±17.49SF-36 Physical Dimension*+48.49±4.8345.61±5.8249.75±2.75SF-36 Psychological Dimension*+43.00±8.1137.03±12.5844.33±7.33Depression*+6.83±7.8312.55±10.775.88±5.19*Significant differences were found between control and intervention group. + Significant differences were maintained between baseline and follow-up assessments. No differences taking into account confounders were observed.Variable changes were maintained in FU participants assessed after 6 months. Correlation between QoL and LTEL (r=0.52; p=0.008) and significant weight loss (χ22=6.08; p=0.048) were observed. Conclusion. These results suggest that a specifically designed BC exercise program increases LTEL, which correlates to a better QoL. This may reduce psychological and physical side effects of systemic treatment in patients with early BC that have recently finished treatments, even producing lifestyle changes in BC patients that could be long lasting. Citation Format: Soraya Casla, Sara López-Tarruella, Yolanda Jerez, Iván Márquez-Rodas, Ricardo Cubedo, Isabel Calvo, Ana Martinez, Sara Cano, Rubén Barakat, Miguel Martín. Exercise intervention to run away from breast cancer treatment side effects: An integrative approach [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-08.

Breast cancer under age 40: a different approach.

Breast cancer (BC) under age 40 is a complex disease to manage due to the additionally fertility-related factors to be taken in consideration. More than 90% of young patients with BC are symptomatic. Women<40 years are more likely to develop BC with worse clinicopathological features and more aggressive subtype. This has been frequently associated with inferior outcomes. Recently, the prognostic significance of age<40 has been shown to differ according to the BC subtype, being associated with worst recurrence-free survival (RFS) and overall survival (OS) for luminal BC. The biology of BC<40 has also been explored through analysis of large genomic data set, and specific pathways overexpressed in these tumors have been identified which can lead to the development of targeted therapy in the future. A multidisciplinary tumor board should determine the optimal locoregional and systemic management strategies for every individual patient with BC before the start of any therapy including surgery. This applies to both early (early breast cancer (EBC)) and advanced (advanced breast cancer (ABC)) disease, before the start of any therapy. Mastectomy even in young patients confers no overall survival advantage when compared to breast-conserving treatment (BCT), followed by radiotherapy. Regarding axillary approach, indications are identical to other age groups. Young age is one of the most important risk factors for local recurrence after both breast-conserving surgery (BCS) and mastectomy, associated with a higher risk of distant metastasis and death. Radiation after BCS reduces local recurrence from 19.5 to 10.2% in BC patients 40 years and younger. The indications for and the choice of systemic treatment for invasive BC (both early and advanced disease) should not be based on age alone but driven by the biological characteristics of the individual tumor (including hormone receptor status, human epidermal growth factor receptor 2 (HER-2) status, grade, and proliferative activity), disease stage, and patient's comorbidities. Recommendations regarding the use of genomic profiles such as MammaPrint, Oncotype Dx, and Genomic grade index in young women are similar to the general BC population. Especially in the metastatic setting, patient preferences should always be taken into account, as the disease is incurable. The best strategy for these patients is the inclusion into well-designed, independent, prospective randomized clinical trials. Metastatic disease should always be biopsied whenever feasible for histological confirmation and reassessment of biology. Endocrine therapy is the preferred option for hormone receptor-positive disease (HR+ve), even in presence of visceral metastases, unless there is concern or proof of endocrine resistance or there is a need for rapid disease response and/or symptom control. Recommendations for chemotherapy (CT) should not differ from those for older patients with the same characteristics of the metastatic disease and its extent. Young age by itself should not be an indication to prescribe more intensive and combination CT regimens over the sequential use of monotherapy. Poly(ADP-ribose) polymerase inhibitors (PARP inhibitors) represent an important group of promising drugs in managing patients with breast cancer susceptibility gene (BRCA)-1- or BRCA-2-associated BC. Specific age-related side effects of systemic treatment (e.g., menopausal symptoms, change in body image, bone morbidity, cognitive function impairment, fertility damage, sexual dysfunction) and the social impact of diagnosis and treatment (job discrimination, taking care for children) should also be carefully addressed when planning systemic long-lasting therapy, such as endocrine therapy. Survivorship concerns for young women are different compared to older women, including issues of fertility, preservation, and pregnancy.

Testicular cancer: biology and biomarkers

The term "human germ cell tumors" (GCTs) refers to a heterogeneous group of neoplasms, all with a defined histological appearance. They have specific epidemiological characteristics, clinical behavior, and pathogenesis. Histologically, GCTs contain various tissue elements, which are homologs of normal embryogenesis. We have proposed a subclassification of GCTs in five subtypes, three of which preferentially occur in the testis. These include teratomas and yolk sac tumors of neonates and infants (type I), seminomas and nonseminomas of (predominantly) adolescents and adults (type II), and spermatocytic seminomas of the elderly (type III). Both spontaneous and induced animal models have been reported, of which the relevance for human GCTs is still to be clarified. Multidisciplinary studies have recently shed new light on the (earliest steps in the) pathogenesis of GCTs, mainly in regard of malignant type II GCTs (germ cell cancer (GCC)). This review discusses novel understanding of the pathogenesis of (mainly) GCC, focusing on identification of informative diagnostic markers suitable for application in a clinical setting. These include OCT3/4, SOX9/FOXL2, SOX17/SOX2, as well as embryonic microRNAs. These markers have been identified through studies on normal embryogenesis, specifically related to the gonads, including the germ cell lineage. Their strengths and limitations are discussed as well as the expected future approach to identify the group of individuals at highest risk for development of a GCC. The latter would allow screening of defined populations, early diagnosis, optimal follow-up, and potentially early treatment, preventing long-term side effects of systemic treatment.

Functional MRI studies in non-CNS cancers

With increasing survival, cognitive problems after systemic treatment for non-CNS cancers are a growing concern. Functional magnetic resonance imaging (fMRI) is a noninvasive neuroimaging technique that has the potential to uncover the neural circuitry underlying cognitive problems after systemic treatment in cancer patients. Here, we provide an in depth review of the 14 fMRI studies that have been published to date on potential neurotoxic side effects of systemic treatment for non-CNS cancers. Cross-sectional studies in breast cancer survivors show a consistent pattern of hypoactivation in prefrontal and parietal brain regions during various executive functioning tasks 5 to 10years after completion of adjuvant chemotherapy that are sometimes associated with worse cognitive performance compared to cancer-specific or no-cancer controls. These findings suggest reduced neural functioning as a result of chemotherapy in brain regions that support cognitive functioning. With regard to episodic memory, hypoactivation at encoding is followed by hyperactivation at retrieval, suggestive of impairments in memory encoding that are compensated by neural hyperactivation to perform adequate memory retrieval. Prospective studies of executive functioning and episodic memory show a more complex picture of hypo- and hyperactivation that is possibly due to various counteracting mechanisms relatively shortly after chemotherapy. Two small studies in prostate cancer patients, finally, provide preliminary evidence for reduced activation in task-relevant brain regions after androgen deprivation therapy, suggestive of reduction of neural function. Statistical correction for multiple comparisons in the reviewed studies is typically quite lenient. We suggest that future studies should preferably include larger sample sizes to allow proper statistical correction for multiple comparisons and include comprehensive neurocognitive tests and multimodal MRI to facilitate the interpretation of the observed fMRI findings.

Identification of factors associated with cancer related fatigue syndrome in disease-free breast cancer patients after completing primary treatment

This study is an analysis of variables associated with women who meet the criteria for after completion of successful primary treatment for breast cancer. This analysis was conducted to identify factors independently associated with cancer related fatigue syndrome using a combined dataset from two non-overlapping studies conducted on similar populations. Participants who were clinically (and radiologically) disease-free, between 3 months and 2 years after treatment, were recruited from a single centre. A diagnostic interview was conducted to ascertain whether they met the criteria for cancer related fatigue syndrome. We analysed a number of treatment, laboratory and questionnaire variables between groups. Those that were significantly different were entered into a logistic model. A total of 278 subjects (105 cases of cancer related fatigue syndrome and 173 controls who did not meet the criteria) were analysed. A number of questionnaire responses were significantly different including all of the European Organisation for the Research and Treatment of Cancer core 30 item quality of life questionnaire (EORTC QLQ c30) and Breast questionnaire 23 item subgroup scores. 11 variables were entered into the final model and 5 were independently associated with cancer related fatigue syndrome: Hospital anxiety and depression scale score, EORTC pain and insomnia scales, breast systemic side effects and plasma sodium. There was, however, no association with demographic or treatment variables. As a conclusion, cancer related fatigue syndrome after treatment is linked with sub-clinical mood pain and subjective sleep disturbance and with the side effects of systemic treatment. This study is unable to determine whether these associations are causal, but they provide a potential target for interventions to manage the symptoms of cancer related fatigue syndrome.

Steroids in the Treatment of Smoke Inhalation Injury

Steroids have been used for decades to treat many chronic lung diseases. The key hypothesis for the use of steroids is to reduce a prolonged and destructive inflammatory response. In addition, glucocorticoids may enhance the responsiveness to beta-agonists (which themselves reduce airway reactivity and mucosal edema).1 The anti-inflammatory effects not only reduce the destructive effects of persistent inflammation, but they may also reduce mast cells and thus inhibit the response to allergens. In smoke inhalation injury the response to the insult may be as damaging as the original injury—so it makes sense that steroids may improve the outcome of inhalation injury. Glucocorticoids may have theoretic advantages but their use is not without risk. A major concern is increased potential for infections in patients already at risk for sepsis. The well-known side effects of systemic treatment have led to the common use of inhaled steroids. The concept is that the drugs are delivered to the site of activity while minimizing the ill effects. There are both local and systemic side effects of inhaled steroids.2,3 Local effects include pharyngitis, dysphonia, reflex cough, bronchospasm, and oropharyngeal candidiasis. Because the lungs are a highly efficient avenue for drug delivery (such as delivery of nicotine in cigarettes) it is not surprising that there are systemic side effects of inhaled corticosteroids (ICS). Inhaled ICS can suppress the hypothalamic-pituitary-adrenal (HPA) axis function even to the point of causingadrenal crisis. In children, suppressed growth velocity (as measured by lower leg length) has been well documented. The delayed growth velocity is reversed with the cessation of the ICS. Patients of all ages may have reduced bone mineral density that increases the risk for fractures and osteoporosis. There are potentialchanges to the skin (thinning and increased bruising) and eyes (increased risks for cataracts and glaucoma) that result from inhaled steroids.

Mast cells and tissue reaction to intraperitoneally implanted polymer capsules

The inflammatory reaction to implanted biomaterials often compromises the clinical usefulness of implantable devices. Dexamethasone, an anti-inflammatory agent, acts on macrophages to decrease production of inflammatory mediators, and on mast cells to prevent degranulation. Systemic administration of dexamethasone (dms) in rats decreases the tissue reaction to intraperitoneally implanted vinyl chloride-acrylic copolymer capsules. Local release of even smaller amounts of dms from a polymeric substrate placed inside an acrylic copolymer capsule may control the tissue reaction while avoiding the undesirable side effects of systemic treatment. Such a system also allows investigation of the local effect of soluble molecules on tissue-material interactions without altering the surface properties of the implant or adding the effect of a releasing material. In the present study, we investigated the effect of dms released from ethylene vinyl acetate (EVAc) rods placed in acrylic copolymer capsules and implanted in the peritoneal cavity of rats. In vitro the release of dms from EVAc rods was quasilinear for 5 weeks. When implanted intraperitoneally into rats, polymer capsules containing EVAc/dms rods generated a tissue reaction that was significantly thinner and featured fewer fibroblast and collagen layers than that around capsules containing pure EVAc rods at all time points studied. The tissue reaction layer was also thinner than that previously described in rats treated systemically with dms. The trabeculae of implants with dms-loaded EVAc rods contained significantly more intact mast cells than implants with EVAc alone, suggesting that degranulation of mast cells is involved in the tissue reaction to intraperitoneal polymer implants.

Evaluation of the atherogenic risk of isotretinoin-induced and etretinate-induced alterations of lipoprotein cholesterol metabolism.

Inverse alterations in plasma levels of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol are recognized side effects of systemic treatment with the synthetic retinoids isotretinoin and etretinate. The mass quotients of total plasma cholesterol and high-density lipoprotein cholesterol as well as low-density lipoprotein cholesterol and high-density lipoprotein cholesterol are well-established predictive risk factors of cardiovascular disease. We evaluated and compared these lipoprotein cholesterol ratios of 80 patients treated systemically with isotretinoin (13-cis-retinoic acid) and 81 patients treated with etretinate (aromatic retinoid). Lipoprotein cholesterol data were derived from 5 lipid studies on isotretinoin, including our own results, and 4 published lipid studies on etretinate. For all isotretinoin and etretinate lipid studies, significant increases in the mean plasma levels of total cholesterol and low-density lipoprotein cholesterol and significant decreases in the mean concentration of high-density lipoprotein cholesterol were demonstrated. In comparison with etretinate, oral isotretinoin gave rise to a nearly twofold percent increase of both lipoprotein cholesterol ratios from pretreatment levels. Furthermore, for isotretinoin, an approximately linear dose-related increase of the ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol could be observed. If sustained over long periods, the mean differential rise of the ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol of 0.92 +/- 0.51 for isotretinoin and 0.56 +/- 0.10 for etretinate indicates an increased risk of cardiovascular disease for both retinoids. Etretinate could be identified as the less harmful retinoid for prolonged oral therapy.

The Present Status of the Adrenal Cortical Hormones as Therapeutic Agents in Oral Conditions

An understanding is required of the physiologic basis for the use of adrenal cortical hormones, their mode of action as anti-inflammatory agents and their influence on the various oral diseases. Mention has been made of some of the many advantages of hydrocortisone as the most important therapeutic agent used in oral conditions. Evaluation of its worth has required the determination of its effectiveness, its safety, and its advantages over other medications. During the few years that the hormone has been used by dentists, it has proved most effective in a variety of oral diseases and, though it has not always provided a cure, it has created an effective approach where none had previously existed. Because of the low dosage usually employed in dentistry, there is no danger of undesirable side effects. Prominent among the advantages of hydrocortisone, therefore, is the frequent improvement, or disappearance within a few days, of oral lesions which have been unresponsive to other forms of therapy. Hormonal therapy is now practicable as an office procedure for most dental practitioners if they follow certain requirements. These are: 1. A reasonable familiarity with the physiologic effects of the hormones and with the disease. 2. Awareness of undesirable side effects of systemic treatment, which depend on the size of the dose of hormone and the duration of treatment. 3. Awareness of contraindications to systemic treatment, such as tuberculosis, hypertension, diabetes mellitus, poor cardiac function and severe mental disorders. 4. Relief of symptoms in hormonal therapy should not be taken as a cure of the disease though all evidence of inflammation may be completely suppressed. 5. The hormone should never be used as the sole agent in the treatment of infections but should be accompanied by properly indicated antibiotic therapy.