High BAX/BCL2 mRNA ratio predicts favorable prognosis in laryngeal squamous cell carcinoma, particularly in patients with negative lymph nodes at the time of diagnosis.

OBJECTIVES: Laryngeal squamous cell carcinoma (LSCC), a common type of head and neck cancer, is associated with high rates of metastasis and recurrence. Therefore, accurate prognostic stratification of LSCC patients based on molecular prognostic tumor biomarkers would definitely lead to a better clinical management of this malignancy. The aim of this study was the investigation of the potential combinatorial prognostic value of BCL2 and BAX mRNA expression in LSCC. DESIGN AND METHODS: Total RNA was isolated from 105 cancerous laryngeal tissue specimens obtained from patients having undergone surgical treatment for primary LSCC. After cDNA preparation, a low-cost, in-house developed, sensitive and accurate real-time quantitative PCR (qPCR) methodology was applied for the quantification of BCL2 and BAX mRNA levels. Then, we carried out a biostatistical analysis to assess the prognostic value of the BAX/BCL2 mRNA expression ratio. RESULTS: High BAX/BCL2 mRNA expression constitutes a favorable prognosticator in LSCC, predicting significantly longer disease-free survival (P=0.011) and overall survival (P=0.014) of patients. More importantly, the significant prognostic value of the BAX/BCL2 mRNA expression appeared to be independent of the histological grade and size of the malignant laryngeal tumor as well as TNM stage, as revealed by the multivariate bootstrap Cox regression analysis. Kaplan-Meier survival analysis demonstrated also that the BAX/BCL2 ratio can stratify node-negative (N0) LSCC patients into two subgroups with significantly different DFS and OS (P=0.021 and P=0.009, respectively). CONCLUSIONS: The BAX/BCL2 mRNA ratio is a putative molecular tissue biomarker in CLL and hence deserves further validation in larger cohorts of LSCC patients.

Prevalence of human papillomavirus infection in Greek patients with squamous cell carcinoma of the larynx.

BACKGROUND/AIM: The causal relation between human papillomavirus (HPV) infection and squamous cell carcinoma (SCC) of the larynx has not been yet clarified. The aim of the present study was to investigate HPV infection in 54 SCC of the larynx and correlate it with patients' epidemiological and clinicopathological data. MATERIALS AND METHODS: Fifty-four biopsies were collected from patients with laryngeal SCC and tested for HPV DNA. Local recurrence analysis was performed at the 2- year follow-up. RESULTS: HPV DNA was detected in 18.5% (10/54) of laryngeal SCC; infection from high risk (hr) HPV and low risk (lr) HPV types was found in 16.7% (9/54) and 1.8% (1/54) of the samples, respectively. HPV 16 was the commonest type detected in 7.5% (4/54). The presence of HPV DNA was significantly associated with the absence of tobacco use (p=0.001) and poorly differentiated tumors (p=0.003). CONCLUSION: This study confirms the prevalence of HPV infection among patients with SCC of the larynx.

Continuation of smoking after treatment of laryngeal cancer: an independent prognostic factor?.

AIM: The aim of the study is to examine if continuation of smoking after treatment is an independent factor affecting the prognosis of laryngeal cancer. MATERIALS AND METHODS: A total of 153 patients met the inclusion criteria for this prospective study, and they were followed up for 12-60 months. Smoking cessation/continuation rates were recorded and associated with disease recurrence and overall patient survival. RESULTS: The recurrence rate was 35.29%. Twenty-five percent of the patients continued smoking after treatment, 75% stopped. Of the patients who quit smoking, 28.69% died during the follow-up period, compared to 52.63% of those who continued (p = 0.0047). The respective recurrence rates were 28.7 and 55.26% (p = 0.0022). A stepwise multivariate Cox regression analysis eliminated potential confounders regarding the overall survival rate and confirmed that time between symptom onset and diagnosis, T and N stage and continuation of smoking after treatment are statistically significant factors. Among them, continuation of smoking was found to have the strongest correlation to the overall survival rate. CONCLUSION: Continuation of smoking after treatment of laryngeal cancer is an independent negative prognostic factor. From a clinical standpoint, all patients with known laryngeal cancer should be strongly encouraged to quit smoking.

Apoptotic and proliferative status in HPV (+) and HPV (-) inverted papilloma patients. Correlation with local recurrence and clinicopathological variables.

Inverted papilloma (IP) is a rare sinonasal benign lesion characterized by aggressive biological behavior. Our aim was to evaluate the expression of various proliferation and apoptotic markers and the presence of HPV genotypes in paraffin sections gathered from surgically treated IP patients. Immunohistochemistry for PCNA, bax, cytochrome c and caspase-8 and flow cytometry for the detection of apoptosis, necrosis and ki67 expression were performed. The identification of various HPV subtypes was achieved by nested PCR amplification. Nasal polyps (NP) and specimens from normal nasal epithelium (NE) were used as controls. PCNA was more frequently expressed in IP compared to NE (p=0.04) and caspase-8 and bax staining were less frequently observed in IP compared to NP (p=0.004 and p=0.01 respectively) and NE (p=0.003 and p=0.01, respectively). IP and NP presented significantly higher Ki67 flow cytometry values compared to NE (p<0.001 and p=0.02 respectively). Cytochrome c was more frequently expressed in IP specimens with more prominent inflammation (p=0.02). A low HPV DNA detection rate was observed. Neither HPV status nor any of the apoptotic or proliferative markers studied was associated with the patients' clinicopathological characteristics. Increased Ki67 appeared to correlate with disease recurrence (p=0.01). Increased PCNA and Ki67 and decreased bax and caspase-8 expression indicate that cell proliferation is increased while apoptosis is inhibited in IP, explaining its biological behavior.

Effect of perioperative immuno-enhanced enteral nutrition on inflammatory response, nutritional status, and outcomes in head and neck cancer patients undergoing major surgery.

Administration of immuno-enhanced nutritional support may decrease postoperative morbidity, mortality, and infectious complications in cancer patients. The aim of this study was to verify that perioperative enteral diet, enriched with the nutrients arginine, ribonucleic acid (RNA), and ω-3 fatty acids improves outcomes of head and neck cancer patients undergoing major surgery. Forty patients with squamous cell carcinoma of the head and neck were studied. Group 1 received no preoperative nutritional support, whereas Group 2 received an oral formula with nutrients arginine, RNA, and ω-3 fatty acids. After surgery, Group 1 received a standard enteral formula, whereas Group 2 received an enriched enteral formula. Albumin (g/dl), prealbumin, fibrinogen, CRP, Il-6, and TNFa were measured 5 days before and 8 days after surgery. No statistically significant difference was observed for all the evaluated markers between postoperative and preoperative levels for both groups. The rate of complications was significantly reduced in the total number of patients receiving immunonutrition and in the particular subgroup of well-nourished patients receiving an immuno-enhanced diet. Perioperative enteral immuno-enhanced feeding in head and neck cancer patients undergoing major surgery may influence the postoperative outcomes by reducing the frequency rate of infections and wound complications.

Hypersensitivity reactions associated with platinum antineoplastic agents: a systematic review.

Platinum-containing chemotherapy agents (cisplatin, carboplatin, oxaliplatin) have been approved in the first-line setting of numerous malignancies, such as ovarian, bladder, head and neck, colorectal, and lung cancer. Their extensive use over the last decade has led to a significant increase in the incidence of hypersensitivity reactions, which are defined as unforeseen reactions whose signs and symptoms cannot be explained by the known toxicity of these drugs. Skin rash, flushing, abdominal cramping, itchy palms, and back pain are common symptoms. Cardiovascular and respiratory complications can prove fatal. Multiple pathogenetic mechanisms have been suggested. Hypersensitivity usually appears after multiple infusions, suggesting type I allergic reactions; however, other types of hypersensitivity also seem to be implicated. Several management options are available to treating physicians: discontinuation of chemotherapy, premedication, prolonging of infusion duration, desensitization protocols, and replacement with a different platinum compound after performing skin tests that rule out cross-reactions among platinum agents.

Acute hypersensitivity reactions to chemotherapy agents: an overview.

Hypersensitivity reactions to chemotherapy agents are defined as unexpected reactions with signs and symptoms not consistent with known toxicity of these drugs. These reactions range from mild to life-threatening and are difficult to predict. Symptoms include flushing, nausea, difficulty breathing, back pain, hypotension and tachycardia. Hypersensitivity is commonly encountered owing to the increasing use of chemotherapy drugs in clinical practice. The pathogenetic mechanisms are not fully understood but they seem to vary between agents. Reactions to taxanes usually occur during the first few minutes of the first or second infusion, whereas acute reactions to platinum agents usually occur after multiple cycles of therapy. Basic principles that allow management and possible completion of the regimen should be followed. Certain protocols aim to prevent acute reactions by slowing the infusion rate and by administering steroid and histamine receptor antagonists. Skin testing and desensitization protocols have also been successfully used in case of hypersensitivity to various chemotherapy drugs. Knowledge of all available management options assists physicians in making the most appropriate decision regarding further treatment.

Bax, cytochrome c, and caspase-8 staining in parotid cancer patients: markers of susceptibility in radiotherapy?

OBJECTIVE: Negative bcl-2 and HLA-DR protein expression have been associated with responsiveness to adjuvant radiotherapy in surgically treated parotid cancer patients. The aim of this study was to investigate the prognostic significance of bax, cytochrome c, and caspase-8 protein expression in a group of surgically treated patients to determine whether they also suggest markers of responsiveness to adjuvant radiotherapy. STUDY DESIGN: Historical cohort study. SETTING: Otolaryngology department in a university hospital. SUBJECTS AND METHODS: The immunohistochemical expression of bax, cytochrome c, and caspase-8 were studied in paraffin-embedded tissue specimens originating from 27 surgically treated parotid cancer patients and nine patients with Warthin parotid tumors (control group) and correlated with the patients' clinicopathological characteristics and clinical outcome. RESULTS: Caspase-8 negative staining was more frequently observed in higher TNM stages and in tumors measuring more than 4 cm (P = 0.009 and P = 0.018, respectively). Caspase-8 (-)/cytochrome c (-) patients carried low-grade lesions without nodal involvement (P = 0.01 and P = 0.05, respectively). Caspase-8 (-) patients who received postoperative radiotherapy presented a significantly increased disease-free survival compared to those who did not (P = 0.04). Patients bearing bax (-) tumors who received postoperative radiotherapy presented an improved four-year disease-free survival compared to bax (-) patients who did not receive any type of adjuvant radiotherapy (P = 0.017). CONCLUSION: Bax, cytochrome c, and caspase-8 protein expression failed to independently predict survival in parotid cancer patients. However, patients with bax (-) or caspase-8 (-) tumors should be considered as candidates for adjuvant radiotherapy in order to achieve better local disease control.

Administration of cisplatin in three patients with carboplatin hypersensitivity: is skin testing useful?

Carboplatin is a chemotherapeutic agent approved in the first-line setting of numerous malignancies. Hypersensitivity to carboplatin has been reported in up to 44% of patients receiving this antineoplastic agent, usually occurring after several courses of treatment. The aim of this study was to determine the usefulness of skin tests in ruling out cross-reaction to cisplatin to continue platinum-based chemotherapy in patients who are responsive to these agents. Prick tests and intradermal tests with a series of dilutions of carboplatin and cisplatin were performed on three patients who had exhibited medium and severe hypersensitivity reactions to carboplatin. Prick tests were negative in both the antineoplastic agents. Intradermal tests with carboplatin were positive in all three patients and negative with cisplatin. In all patients, the administration of cisplatin instead of carboplatin was well tolerated without the need of premedication. In conclusion, intradermal skin tests can be a useful tool for detecting a potential cross-reaction between platinum salts. It allows safe administration of a different platinum agent in patients who seem to benefit from platinum-based therapy. Discontinuation of chemotherapy, desensitization protocols and steroid premedication can be avoided.

Congenital aural atresia reconstruction: a surgical procedure with a long history.

BACKGROUND: Pinna deformities, combined with congenital aural atresia, have been a matter of serious debate in the literature as they are associated with major aesthetic and functional problems that are difficult to manage. These problems have been described as early as 2000 BC. The aim of the present article is to approach the whole problem as one (pinna malformation and aural atresia) and present the history as well as the current approaches in reconstruction. METHODS: Extensive literature search and medical history books were used as scientific sources. RESULTS: For many centuries, the prevalent view was that any surgical attempts to reconstruct the pinna and the ear canal were of little value. In addition, the aesthetic result of these early surgical procedures was mostly unacceptable. Over time, new surgical techniques and synthetic materials were used, leading to satisfactory and lasting aesthetic and functional results in selected patients, improving their quality of life, while reducing the complication rate. However, many cases are still challenging for plastic surgeons and ENT surgeons alike. CONCLUSIONS: Despite significant progress in the field, surgery for pinna deformities combined with congenital aural atresia still remains one of the most challenging and risky procedures. Accurate audiological evaluation of newborns as well as assessment of their craniofacial development is necessary and can help the plastic surgeons and otologists choose proper candidates for surgical repair and a suitable and age-appropriate therapeutic plan. History and repeated failures have taught us that close multidisciplinary approach is of paramount importance.

Primary localized laryngeal amyloidosis presenting with hoarseness and dysphagia: a case report.

INTRODUCTION: Primary localized laryngeal amyloidosis is an extremely rare condition. It usually presents with hoarseness, pain and/or difficulty in breathing. CASE PRESENTATION: We present the case of a 23-year-old woman with primary localized laryngeal amyloidosis who presented with hoarseness and dysphagia. CONCLUSION: A search of PubMed shows that dysphagia in patients with laryngeal amyloidosis has been reported only once, although this symptom is relatively common in other conditions presenting with laryngeal mass. There were no signs of any systemic disease in our patient and diagnosis was established histopathologically. She was treated surgically by microlaryngoscopy under general anesthesia and the mass was excised using a CO(2) laser technology method.

Cell adhesion molecules: role and clinical significance in cancer.

There is a growing body of evidence suggesting that alterations in the adhesion properties of neoplastic cells endow them with an invasive and migratory phenotype. Indeed, changes in the expression or function of cell adhesion molecules have been implicated in all steps of tumor progression, including detachment of tumor cells from the primary site, intravasation into the blood stream, extravasation into distant target organs, and formation of the secondary lesions. This review presents recent data regarding the role of cell adhesion molecules in tumor development and progress with concern to their clinical exploitation as potential biomarkers in neoplastic diseases.

Supracricoid hemilaryngopharyngectomy for selected pyriform sinus carcinoma patients--a retrospective chart review.

BACKGROUND: The aim of this study is to assess the functional and oncologic results of supracricoid hemilaryngopharyngectomy and report our experience in the technique, local control and overall survival rates. MATERIALS AND METHODS: 18 selected patients with pyriform sinus cancer treated by supracricoid hemilaryngopharyngectomy in a University Hospital setting. Retrospective chart review was used to assess functional and oncologic results of the procedure. RESULTS: The actuarial 5 year survival rate in our study was 55.56% and the actuarial neck recurrence rate was 16.67%. All patients were successfully decannulated. Aspiration pneumonia was the most common postoperative complication (22.23%) and was treated mostly conservatively. One patient required a temporary gastrostomy but no patient needed total laryngectomy in the postoperative period. CONCLUSION: Supracricoid hemilaryngopharyngectomy in experienced hands is a reliable technique for selected patients with pyriform sinus cancer.

Use of rituximab in combination with conventional chemotherapy for the treatment of non-Hodgkin's lymphoma of the head and neck.

BACKGROUND: Rituximab, an anti-CD20 chimeric monoclonal antibody that specifically depletes mature B cells, is an effective single agent in the treatment of relapsed or refractory indolent lymphomas, and has been shown to improve the survival rate of elderly patients with diffuse large-B-cell lymphoma when used in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). PATIENTS AND METHODS: The combined effect of rituximab and CHOP has been comparatively studied against CHOP alone in 18 elderly patients with non-Hodgkin's lymphoma of the head or neck treated in the 1st Department of Otolaryngology at Hippokration Hospital between January 1998 and January 2004. RESULTS: Response rates were 91% and 100% in patients treated with rituximab plus CHOP and with CHOP alone, respectively. Overall survival and disease-free survival rates were 91% in the rituximab plus CHOP group, compared with 83% and 60%, respectively, in the CHOP alone group (p=0.75 and p=0.24 for the differences between the groups, respectively). The rituximab plus CHOP therapy was generally well tolerated, with few adverse events reported. CONCLUSION: The results of this small case series, although not statistically significant, suggest that rituximab in combination with CHOP may represent an effective treatment option for elderly patients with non-Hodgkin's lymphoma of the head and neck.

Head and neck cancer in the elderly: an overview on the treatment modalities.

The percentage of elderly people with head and neck cancers (HNC) is rising due to increasing average lifespan. As with younger patients, elderly patients require a multidisciplinary approach in order to optimise treatment results. The biological, not the chronological, age should be defined individually based on co-morbidities and performance status. A comprehensive geriatric assessment represents the first and essential step for selecting further treatment options. Major improvements have been accomplished in surgical techniques and radiotherapy delivery. Several chemotherapeutic agents and targeted therapies with different toxicity profile are also available. However, the randomised studies that defined the nature of these improvements included only a small proportion of patients older than 65 years. In deciding which treatment strategy would be suitable for an individual elderly patient, we review the literature regarding surgery, radiotherapy, and chemotherapy or their various combinations.

BCL-2, p53 and HLA-DR antigen expression in surgically treated parotid cancer patients.

Our objective was to investigate the prognostic significance of bcl-2 protein, p53 protein and HLA-DR antigen expression in a group of surgically treated parotid cancer patients. We studied bcl-2, p53 and HLA-DR immunohistochemical expression in paraffin-embedded surgically removed tissue specimens derived from 26 patients with parotid cancer and 9 patients with Warthin parotid tumors operated between 2000 and 2006 at the Hippokration Hospital of Athens. The staining results were correlated with the patients' clinicopathological characteristics and clinical outcome. Bcl-2 expression was associated with a significantly decreased survival in patients with advanced tumor stage (P = 0.04), high grade lesions (P = 0.02), or cervical node involvement (P = 0.03). Radiotherapy was associated with a significantly improved recurrence-free survival among patients with negative tumor staining for either bcl-2, or both HLA-DR and bcl-2 [HLA-DR(-)/Bcl-2(-)] (P = 0.04 for both comparisons). Classical clinicopathologic factors failed to show prognostic value both in the univariate and the multivariate analyses performed. Our results suggest that bcl-2 can be used to identify locally advanced or histologically aggressive tumors with a lower survival probability following the application of standard treatment modalities. Furthermore, bcl-2(+) patients should be considered for more aggressive adjuvant treatment protocols, since conventional radiotherapy often fails to decrease relapse rates in this setting of patients.

Resection of giant ethmoid osteoma with orbital and skull base extension followed by duraplasty.

BACKGROUND: Osteomas of ethmoid sinus are rare, especially when they involve anterior skull base and orbit, and lead to ophthalmologic and neurological symptoms. CASE PRESENTATION: The present case describes a giant ethmoid osteoma. Patient symptoms and signs were exophthalmos and proptosis of the left eye, with progressive visual acuity impairment and visual fields defects. CT/MRI scanning demonstrated a huge osseous lesion of the left ethmoid sinus (6.5 cm x 5 cm x 2.2 cm), extending laterally in to the orbit and cranially up to the anterior skull base. Bilateral extensive polyposis was also found. Endoscopic and external techniques were combined to remove the lesion. Bilateral endoscopic polypectomy, anterior and posterior ethmoidectomy and middle meatus antrostomy were performed. Finally, the remaining part of the tumor was reached and dissected from the surrounding tissue via a minimally invasive Lynch incision around the left middle canthus. During surgery, CSF rhinorrhea was observed and leakage was grafted with fascia lata and coated with bio-glu. Postoperatively, symptoms disappeared. Eighteen months after surgery, the patient is still free of symptoms. CONCLUSION: Before management of ethmoid osteomas with intraorbital and skull base extension, a thorough neurological, ophthalmological and imaging evaluation is required, in order to define the bounders of the tumor, carefully survey the severity of symptoms and signs, and precisely plan the optimal treatment. The endoscopic procedure can constitute an important part of surgery undertaken for giant ethmoidal osteomas. In addition, surgeons always have to take into account a possible CSF leak and they have to be prepared to resolve it.

Myofascial pain syndromes in the maxillofacial area: a common but underdiagnosed cause of head and neck pain.

Myofascial pain syndromes (MPS) are a large group of muscular disorders, characterized by the presence of hypersensitive spots called trigger points (TP). The maxillofacial region is a high-frequency area for developing TPs. The aim of this paper was to review and summarize the most important methods of management. A literature review was carried out from Medline and database sources. A range of study types were selected for analysis. TP formation and activity result in a reverberating circuit of sustained neural activity. Central mechanisms, primarily associated with psychosocial factors, lead to chronicity. Other synergistic factors are metabolic disorders, nutritional imbalances and regional anatomic disorders. A detailed history and physical examination are important for proper diagnosis. The aim of MPS management is pain relief and restoration of full muscle function. Treatment may require enhancing central inhibition, using pharmacological and/or behavioural techniques, and reducing peripheral inputs, using physical therapy. There are various effective methods of inactivation of TPs. Recognition and reduction of synergistic factors may be important. MPS have a very high prevalence in the general population, despite low awareness among physicians, affecting patients' quality of life. There is a need for interdisciplinary teams of health professionals to achieve proper diagnosis, management and sustainable outcomes.

Treating common problems of the nose and throat in pregnancy: what is safe?

Although all kinds of medications should be avoided during pregnancy, the majority of pregnant women receive at least one drug and 6% of them during the high-risk period of the first trimester. The aim of the present paper is to discuss the appropriate management of rhinologic and laryngeal conditions that may be encountered during pregnancy. A literature review from Medline and database sources was carried out. Related books and written guidelines were also included. Controlled clinical trials, prospective and retrospective studies, case-control studies, laboratory studies, clinical and systematic reviews, metanalyses, and case reports were analysed. The following drugs are considered relatively safe: beta-lactam antibiotics (with dose adjustment), macrolides (although the use of erythromycin and clarithromycin carries a certain risk), clindamycin, metronidazole (better avoided in the first trimester), amphotericin-B (especially in immunocompromised situations during the second and third trimester) and acyclovir. First-line antituberculous agents isoniazid, ethambutol, pyrazinamide, and ciprofloxacine in drug-resistant tuberculosis can be also used. Non-selective NSAIDs (until the 32nd week), nasal decongestants (with caution and up to 7 days), intranasal corticosteroids, with budesonide as the treatment of choice, second generation antihistamines (cetirizine in the third trimester, or loratadine in the second and third trimester), H2 receptor antagonists (except nizatidine) and proton pump inhibitors (except omeprazole) can be used to relieve patients from the related symptoms. In cases of emergencies, epinephrine, prednisone, prednisolone, methylprednisolone, dimetindene and nebulised b(2) agonists can be used with extreme caution. By contrast, selective COX-2 inhibitors and BCG vaccination are contraindicated in pregnancy. When prescribing to a pregnant woman, the safety of the materno-foetal unit is considered paramount. Although medications are potentially hazardous, misconceptions and suboptimal treatment of the mother might be more harmful to the unborn child. Knowledge update is necessary to avoid unjustified hesitations and provide appropriate counselling and treatment for pregnant women.

Treating common ear problems in pregnancy: what is safe?

In everyday practise, more than 80% of pregnant women receive one at least medication, often for ENT causes. The aim of the present paper is to review the literature on safety and administration of medical treatment for ear diseases, in pregnant women. The literature review includes Medline and database sources. Electronic links, related books and written guidelines were also included. The study selection was as follows: controlled clinical trials, prospective trials, case-control studies, laboratory studies, clinical reviews, systematic reviews, metanalyses, and case reports. The following drugs are considered relatively safe: beta-lactam antibiotics (with dose adjustment), macrolides (although the use of erythromycin and clarithromycin carries a certain risk), and acyclovir. Non-selective NSAIDs (until the 32nd week), nasal decongestants (with caution and up to 7 days), intranasal corticosteroids, with budesonide as the treatment of choice, first generation antihistamines, or cetirizine (third trimester) and loratadine (second and third trimester) from the second generation, H2 receptor antagonists (except nizatidine) and proton pump inhibitors (except omeprazole), can be used to relieve patients from the related symptoms. Meclizine and dimenhydrinate, as antiemetics in vertigo attacks; metoclopramide, vitamin B6 and ginger rhizome, alternatively. Low-dose diazepam and diuretics in severe cases of Meniere's disease (with caution). Systemic administration of prednisone and prednisolone can be considered in selected cases. By contrast, selective COX-2 inhibitors, betahistine and vasodilating agents are contraindicated in pregnancy. Since otologic and neurotologic manifestations during pregnancy tend to seriously affect the quality of life of the expectant mothers, ENT surgeons should familiarise themselves with the basic guidelines and safety precautions for any related medication, in order to provide appropriate treatment.