Relationship between amikacin blood concentration and ototoxicity in low birth weight infants.

Amikacin (AMK) is used as empiric therapy for severe infections such as sepsis in low birth weight (LBW) infants. AMK administered once daily (OD) in adults is reported to be therapeutically effective and prevent side effects, however, evidence on AMK administration in LBW infants is limited, with no clear indications of effectiveness. We performed therapeutic drug monitoring analysis of 20 infants treated with AMK OD for severe infections such as bacteremia. Treatment effectiveness was admitted by the patients' medical records, and side effects of renal dysfunction and ototoxicity were investigated. The mean gestational age was 30.4 ± 5 weeks and mean body weight (Bw) was 1280.2 ± 809.8 g. The mean AMK dose was 14.1 ± 2.6 mg/kg and mean administration period was 10.1 ± 4.1 days. Blood concentration was measured 6.3 ± 2.3 days after AMK administration; mean peak and trough concentrations were 29.1 ± 7.5 µg/mL and 7.6 ± 6.9 µg/mL, respectively. Additionally, therapeutic effect was observed in all patients, and no significant change in serum creatinine (CRE) concentration (a marker of renal dysfunction) was observed, suggesting no renal dysfunction. Ototoxicity was observed in 4 patients, 3 of whom had trough concentrations ≥10 µg/mL. When we categorized patients into two groups using a trough cut-off value of 10 µg/mL, no difference in AMK dose was observed. However, there were significant differences in peak concentration, Bw, volume of distribution and CRE. Our findings suggest AMK trough concentration ≥10 µg/mL significantly affects ototoxicity in neonates.

Efficacy and adverse events of oral isotretinoin for acne: a systematic review.

Despite many years of clinical use of isotretinoin, a comprehensive review of evidence for isotretinoin therapy in patients with acne is lacking. We searched MEDLINE, Embase, Cochrane Central, relevant web pages and bibliographies for randomized controlled trials in acne evaluating isotretinoin vs. control (placebo or other therapy). Data were extracted and summarized descriptively. Eleven trials were identified (total 760 patients randomized), containing mostly men. Mean treatment ages ranged from 18 to 47·9 years and participants generally had moderate-to-severe acne. Across all trials, isotretinoin therapy reduced acne lesion counts by a clinically relevant amount, and always by a greater amount than control, which was either placebo (two studies), oral antibiotics (seven studies) or other control (two studies). Across trials with an overall low risk of bias, two of three demonstrated statistically significant differences between isotretinoin and control. The frequency of adverse events was twice as high with isotretinoin (751 events) than with control (388 events). More than half of all adverse events were dermatological and related to dryness. Adverse events from isotretinoin causing participant withdrawal from trials (12 patients) included Stevens-Johnson syndrome, cheilitis, xerosis, acne flare, photophobia, elevated liver enzymes, decreased appetite, headaches and depressed mood. This review suggests that isotretinoin is effective in reducing acne lesion counts, but adverse events are common. This study was registered with PROSPERO number CRD42015025080.

Otorhinolaryngological Toxicities of New Drugs in Oncology.

Many new or relatively new cancer drugs-personalized anticancer agents-have been approved for use in various clinical settings in oncology or are still under evaluation in clinical trials. Targeted therapies as well as new immune checkpoint blockers have toxicity profiles that differ from conventional cytotoxic chemotherapy, and many can cause adverse effects that affect the mouth and pharynx, the nasal cavities, and the larynx. This review aims to provide an overview of current knowledge concerning these side effects and contemporary management. Adverse effects of the mouth/pharynx, nasal cavities, larynx, and cochlear-vestibular system are generally low grade (according to the Common Terminology Criteria for Adverse Events) and generally present non-life-threatening symptoms. However, the impact on patients' quality of life could be important. The incidence and severity vary according to the drug, its target(s), and dose, but there are currently no known predictive factors, and each patient has an individual toxicity profile. Management guidelines are based on expert opinion. These ear, nose, and throat adverse effects are not frequently mentioned in the literature because of the often non-specific nature of the symptoms and their mildness, but also the absence of specific treatment. These symptoms can contribute to decreased quality of life and lead to drug compliance issues if not diagnosed and managed appropriately.

Angioedema: 6 years experience with fourteen cases.

OBJECTIVE: To study the difference in the findings between the causes of angioedema and the characteristics of angioedema induced by angiotensin receptor II blockers (ARBs), and to investigate whether laboratory examinations for acute phase inflammatory markers can aid in diagnosis and predict airway risk. METHODS: We retrospectively reviewed fourteen cases of patients with angioedema that were treated from 2000 to 2006. Data were collected regarding age, sex, location of the edema, cause, time course of resolution and laboratory examinations (leukocyte counts, serum C-reactive protein (CRP) level, complement function and the activity of C1 esterase inhibitor). RESULTS: The causes of angioedema were ACEIs in six patients (42.9%), candesartan (ARB) in three (21.4%), HAE (types 1 and 2) in two, and unknown in three. Of these patients, 71.4% exhibited edema in the floor of the mouth, irrespective of the cause. Two patients with edema induced by candesartan exhibited both lingual and laryngeal edemas. The remaining one with candesartan-induced edema exhibited edema in the neck and mediastinum and pleural effusion. The average time to resolution was 4.1 days, ranging from one to twelve days. The edema in eleven patients resolved with conservative therapy, while three patients underwent tracheotomy. In two patients with candesartan-induced edema, although the edemas resolved completely after cessation of candesartan administration, the edemas reappeared in the same locations, two and thirty days after the cessation of candesartan for each patient. None of the patients with angioedema induced by ACEIs exhibited elevation of serum CRP levels. No significant differences were found for leukocyte counts and serum CRP levels between patients with angioedemas induced by ACEIs, ARB and those of unknown cause. No significant differences were observed in the above findings between the patients who underwent tracheotomy and those who did not. Two patients exhibited low C4 levels, and one of the two exhibited no activity of C1 esterase inhibitor. CONCLUSION: Consistent with previous reports, angioedema in the floor of the mouth extending to the tongue should be considered as a possible risk factor for airway compromise. Laboratory examinations for acute phase inflammatory markers are not useful for diagnosis and are not predictive for airway intubation and tracheotomy. Angioedema induced by candesartan can present in anomalous sites and reappear following drug cessation even if the edema has resolved completely.

Analysis of recurrent angiotensin converting enzyme inhibitor-induced angioedema.

OBJECTIVE/HYPOTHESIS: A known risk for patients taking angiotensin converting enzyme-inhibitors (ACE-Is) is angioedema that can involve the face, lips, oral cavity, and larynx. Such upper airway obstruction may be severe enough to require an emergency department visit or even necessitate prompt airway intervention. Once a patient has had an episode of ACE-inhibitor induced angioedema (AIIA), certainly a thrust of continuing case management would be to avoid the occurrence of subsequent episodes of AIIA that potentially can be life-threatening. Nevertheless, recurrent episodes of AIIA do occur. This study aims to characterize a patient's risk for recurrent AIIA, determine the cause for repeat episodes of AIIA and recommend steps to be taken to minimize the recurrence of AIIA. STUDY DESIGN: Retrospective study. METHODS: A retrospective chart review of all patient encounters at our medical center between January 1, 1991 and December 30, 2005 with a diagnosis of angioedema was performed. The documented etiology of the angioedema, comorbidities, and documentation of an "allergy" to ACE-I were noted. Observations regarding risk factors for recurrent AIIA were made. RESULTS: Recurrent AIIA occurred in 23 patients with a recurrence rate of 6.2%. Risk factors for recurrence were categorized as patient factors, physician factors, or systems factors. Physician error with failure to document in the medical record, the suspicion of AIIA, and failure to consider risk in prescribing ACE-I after an episode of angioedema had occurred were the most common causes of recurrent AIIA. CONCLUSIONS: Angioedema can cause life-threatening airway compromise yet patients with a history of one episode of AIIA are at risk for a subsequent episode. Physicians can modify clinical practices to avert the potentially life-threatening side effects of ACE-inhibitors in patients with a prior episode of AIIA.

[Analgesic intolerance (AI). Key position of ENT physicians for early detection of this condition]. / Analgetika-Intoleranz. Schlüsselposition von HNO-Arzten bei der Früherkennung des Krankheitsbildes.

The clinical manifestation of analgesic intolerance (AI) is frequently associated with symptoms examined by ear-nose-throat (ENT) specialists. The prevalence of AI is reported in the literature to be 0.6-2.5%. Even though there are no concluding results concerning its pathogenesis, an altered arachidonic acid metabolism is most likely the underlying pathomechanism. The symptoms include chronic rhinosinusitis with nasal polyps, asthma, gastrointestinal ulcers, angioedema, and urticaria. Clinical reactions after ingestion of nonsteroidal anti-inflammatory-drugs (NSAIDs) are often obvious in the progress of disease. In order to initiate early therapy and therefore prevent the progress of disease, the diagnosis of AI should occur before the complete picture of AI is obvious. Adaptive desensitization is currently the single causal therapy. Frequency of endonasal revision surgery is reduced after desensitization; severe asthma and reactions after ingestion of NSAIDs are avoided. ENT specialists are particularly in a key position for early detection of AI.

[Allergies in ENT]. / Les allergies en ORL.

Allergy is quite frequent and ENT syptoms are usually the visible part of a general disease. Questioning remains the most important part of the enquiry for clinical examination is usually poor if notdesapointing. Biological testings detailed in this paper may be of some help; In Africa, test-treatements using cheap and unharmfull drugs give often the best evidence of allergy. Seldom, ENT allergy may be or become life-threatening. Its detection and appropiate actions are briefly mentioned.

Side effects due to primary antituberculosis drugs during the initial phase of therapy in 1149 hospitalized patients for tuberculosis.

OBJECTIVE: Side effects of the most commonly used primary antituberculosis (anti-TB) drugs may be mild as well as fatal. The aim of this study was to evaluate the side effects of and the risk factors for developing side effects against anti-TB drugs. PATIENTS AND METHODS: Records of 1149 patients with established tuberculosis who initially received anti-TB therapy were evaluated retrospectively. The major side effects, which resulted in a definitive termination from 1 or more drugs related to anti-TB therapy, and the risk factors associated with these side effects, were analyzed. RESULTS: Ninety-five patients (8.3%), constituting 104 cases in total, experienced side effects. Although the frequency of drug reactions were increased from 0.6% at ages <20 to 5.2% at ages 20-40, no gender or age differences were observed between patients who did and did not have side effects. While asymptomatic liver function disturbance was established in 56 of the patients (4.9%) with initiation of anti-TB therapy, the rate of hepatotoxicity was found to be 2.4% in this present study. No age or gender differences were observed among those who had hepatotoxicity and who had not. The major side effects were ototoxicity (1.7%), hepatotoxicity (0.8%), neuropsychiatric manifestations (0.7%), and hyperuricemia (0.6%). CONCLUSIONS: It must be remembered that severe side effects associated with anti-TB drugs were encountered with different frequencies especially among patients hospitalized for pulmonary tuberculosis, and these patients should be followed up by closer monitoring for side effects related to anti-TB drugs.

[ACE inhibitor-induced angioedema in the head and neck region. A matter of time?]. / Durch ACE-Hemmer induziertes Angioödem des Kopf-Hals-Bereichs. Eine Frage der Zeit?

BACKGROUND: Angioedema in the head and neck region is potentially life-threatening and may occur as a side effect of inhibitors of the angiotensin-converting-enzyme (ACEI). So far, little is known about the time between the first application of ACEI and the occurrence of angioedema, or of possible cofactors and laboratory changes. MATERIAL AND METHODS: A total of 21 patients with angioedema during the course of ACEI treatment were compared to 11 patients with angioedema of unknown cause. These were retrospectively analysed for the following criteria: (1) duration of ACEI medication, (2) leading and concomitant diseases, (3) history of allergies, (4) co-medication, (5) laboratory changes, (6) treatment success, and (7) manifestation of recurrent episodes. RESULTS: The mean interval between the initiation of ACEI therapy and the first occurrence of angioedema exceeded 2 years. Values for the acute phase proteins C-reactive protein (CRP) and fibrinogen were significantly increased in the ACEI group compared to the control group. CONCLUSIONS: In any case of angioedema in the head and neck region, a side effect of ACEI must be taken into consideration even if the medication has been taken for months or years.

Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia.

OBJECTIVES: To study the efficacy and safety of dutasteride, a dual inhibitor of the 5-alpha-reductase isoenzymes types I and II. METHODS: A total of 4325 men (2951 completed) with clinical benign prostatic hyperplasia, moderate to severe symptoms (American Urological Association-Symptom Index score of 12 points or greater), a peak flow rate of 15 mL/s or less, a prostate volume of 30 cm3 or greater (as measured by transrectal ultrasonography), and a serum prostate-specific antigen level of 1.5 to 10.0 ng/mL (inclusive) were enrolled into three identical clinical trials and randomized to 0.5 mg dutasteride daily or placebo. After a 1-month, single-blind, placebo lead-in, patients were followed up for 24 months in a double-blind trial with multiple interval assessments. RESULTS: At 24 months, serum dihydrotestosterone was reduced from baseline by a mean of 90.2% (median -93.7%; P <0.001), and the total prostate and transition zone volumes were reduced by a mean of 25.7% and 20.4%, respectively (P <0.001). The symptom score was improved by as early as 3 months, with pooled significance from 6 months onward (P <0.001) and a reduction of 4.5 points (21.4%) at 24 months (P <0.001). The maximal flow rate improved significantly from 1 month (P <0.01), with an increase of 2.2 mL/s reported at 24 months (P <0.001). Hence, the risk reduction of acute urinary retention was 57% and the risk reduction of benign prostatic hyperplasia-related surgical intervention was 48% compared with placebo. The drug was well tolerated. CONCLUSIONS: Dutasteride is a potent inhibitor of dihydrotestosterone production that is safe and effective in terms of the reduction of prostate volume and symptoms, flow rate improvement, and the reduction of the risk of acute urinary retention and surgery during a 24-month study period.

Changing trends in angioedema.

Angioedema can be a life-threatening event presenting to otolaryngologists, emergency medicine physicians, and other physicians. Recent reports suggest an increasing role of angiotensin-converting enzyme inhibitors (ACEIs) in the causation of angioedema. Sixty-four cases occurring between 1994 and 1998 were identified and examined retrospectively. Fifty-eight percent of patients presenting with angioedema were using ACEIs. Ninety-four percent of patients overall, and 92% of patients with ACEI-associated angioedema, were African-American. Tongue, lip, facial, and supraglottic edema were most common. Treatment included intubation in 13% and intensive care unit monitoring in 20%. Nearly all patients were treated with corticosteroids and antihistamines. There were no deaths. Angioedema associated with ACEI use appears to be much more common than previously reported. African-American patients may be at higher risk for angioedema with ACEI use. Successful management was achieved with observation, expectant airway management, corticosteroids, and discontinuation of ACEIs. Patients without airway obstruction or pharyngeal or laryngeal edema who improved with treatment and observation were successfully treated as outpatients.

Effects of air pollution on the upper aerodigestive tract.

The main route of contamination of the human body with airborne pollutants is through the upper air and food passages. Because of the delicate balance of the mucous membranes and special sensory organs of these passages with respect to mucociliary activity, local and recruited immune responses, rapid uptake of chemicals, and carcinogenic potential, the ingestion or inhalation of pollutants in the air can be harmful to these internal body barriers. The particular target organs for air pollution effects on the upper aerodigestive tract include the mucosa, olfactory epithelium, auditory receptor cells, glottic epithelium, and adjacent neural and muscular tissues. Hearing loss caused by noise exposure may be aggravated by the concomitant inhalation of solvents. The strongest evidence for the carcinogenic effect of occupational inhalants in the nasal cavity and paranasal sinuses is seen with exposure to hardwood dust, tobacco smoke, furniture making, and leather tanning. With the exception of tobacco smoke, which produces squamous cell carcinomas, the majority of the occupationally related cancers are adenocarcinomas, usually of the intestinal variety. Tobacco smoke, passive or active, may lead to end-artery obliteration at the level of the otic end organ, causing a progressive sensorineural hearing loss. Further environmental research in the upper aerodigestive tract should aim at developing biologic markers to determine early, premalignant tissue changes; identifying the effects of chronic, low-dose toxic exposure on mucous membranes and neurosensory organs; providing field-tested tools for the standardized screening of large at-risk populations.

[Occupational hygiene in production and use of multicomponent metal compounds]. / Gigiena truda pri poluchenii i primenenii mnogokompozitsionnykh soedinenii metallow.

The article deals with results obtained in hygienic evaluation of production and application of new monocrystalline compounds based on cesium, sodium, iodine, lead, scandium, fluorine. The evaluation covered work conditions and health state of those engaged into production of monocrystalline compounds, revealed the main occupational hazards. The experiments determined fundamental toxicometric parameters, studied characteristics of general toxic and specific effects induced by lead fluoride and cesium iodine. The results formed basis for sanitary measures, establishment of MACs for 4 monocrystalline compounds in the air of workplace.

Chemical mixtures exposure and children's health.

Studies to examine the health of the children with compromised immune and endocrine systems living in different air polluted regions by oil waste were undertaken. A dose-dependent effects of the anthropogenic pollution on the functional immunocompetent cells activity, mainly T-suppressors was observed as well as stimulation of immunoglobulins synthesis and reduction of phagocytic activity of neutrophils. Disconnection of immunoglobulins synthesis with production of high specifity antibodies, antiviral in particular, was registered. Correlation changes between indices of hormonal activity and humoral specific defence leading to an increase in the role of peripheral hormones with immune inhibitory effect were revealed. The informative value of studied indices as environmental pollution bioindicators was considered. They will stimulate further investigations in biomonitoring and its introduction into practice of ecological expertise of dwelling agglomerations.

[Otorhinolaryngologic symptoms caused by the intranasal abuse of cocaine. Report of a case]. / Manifestaciones otorrinolaringológicas por el abuso intranasal de cocaína. A propósito de un caso.

Cocaine abuse is associated with medical complications that depends on the route of administration. Intranasal "snorting" is associated with complications secondary to chronic irritation on the nasal mucosa. A case of long-standing intranasal cocaine abuse is presented with unusual complications: septal and palatal necrosis, osteolytic sinusitis and bilateral optic neuropathy. The CT scan demonstrated a soft-tissue mass in etmoid and sphenoidal sinus and orbits. The histopathologic examination revealed a nonspecific pattern of chronic inflammation with no evidence suggestive of infection, neoplasm or lethal midline granuloma. The case had a fatal outcome. Because of the constellation of singular manifestations we discuss the differential diagnosis. Interdisciplinary approach is stressed. Emphasis is made in early diagnosis.