Challenging a paradigm: skin sensitivity to sodium lauryl sulfate is independent of atopic diathesis.

BACKGROUND: Sodium lauryl sulfate (SLS) is the best-studied detergent in irritant contact dermatitis. In atopic dermatitis, the two major pathophysiological abnormalities concern skin barrier function and regulation of cutaneous immune responses. The probability of atopic skin diathesis can be assessed by comprehensive analysis of patient history, as well as clinical and laboratory findings, resulting in the Erlangen Atopy Score (EAS). OBJECTIVES: To investigate the impacts of (i) atopic skin diathesis according to the EAS and (ii) the physician-assessed diagnoses 'atopic dermatitis', 'allergic rhinitis' and 'allergic asthma' on SLS skin reactions. METHODS: This is a retrospective analysis of data from 2030 consecutive patients patch tested with SLS (0·25% aqueous) from two tertiary referral centres in Germany, from 2008 to 2014. RESULTS: Patients with a high probability of atopic skin diathesis showed no significant increase in positive SLS reactions compared with patients without atopic skin diathesis (14·2% vs. 16·8%). The grading of positive SLS skin reactions (1-4) revealed no differences in patients with or without atopic skin diathesis. Furthermore, diagnoses of atopic dermatitis, allergic rhinitis or allergic asthma had no impact on positive SLS skin reactions in multivariate logistic regression analysis. CONCLUSIONS: We found no association of increased skin irritability to SLS with atopic skin diathesis, atopic dermatitis, allergic rhinitis or allergic asthma in a large patient cohort. It therefore seems that the test of skin irritability with SLS, which is currently common practice in many centres, does not allow prediction of susceptibility to irritant eczematous inflammation in atopic vs. nonatopic individuals. What's already known about this topic? Irritant contact dermatitis and atopic skin diathesis share impaired skin barrier function as a pathophysiological pattern. Sodium lauryl sulfate (SLS) is tested at 0·25% aqueous as an irritant control in patch testing, and hence the results might be affected by atopic skin diathesis. What does this study add? Challenging a long-standing paradigm, we found no association of increased reactivity to SLS patch tests in individuals with atopic skin diathesis, atopic dermatitis, allergic rhinitis or allergic asthma in a large patient cohort. Thus, irritant control testing with SLS, which is useful in interpreting doubtful allergen patch test results, does not depend on individual atopy status.

The genetic basis for most patients with pustular skin disease remains elusive.

BACKGROUND: Rare variants in the genes IL36RN, CARD14 and AP1S3 have been identified to cause or contribute to pustular skin diseases, primarily generalized pustular psoriasis (GPP). OBJECTIVES: To better understand the disease relevance of these genes, we screened our cohorts of patients with pustular skin diseases [primarily GPP and palmoplantar pustular psoriasis (PPP)] for coding changes in these three genes. Carriers of single heterozygous IL36RN mutations were screened for a second mutation in IL36RN. METHODS: Coding exons of IL36RN, CARD14 and AP1S3 were sequenced in 67 patients - 61 with GPP, two with acute generalized exanthematous pustulosis and four with acrodermatitis continua of Hallopeau. We screened IL36RN and AP1S3 for intragenic copy-number variants and 258 patients with PPP for coding changes in AP1S3. Eleven heterozygous IL36RN mutations carriers were analysed for a second noncoding IL36RN mutation. Genotype-phenotype correlations in carriers/noncarriers of IL36RN mutations were assessed within the GPP cohort. RESULTS: The majority of patients (GPP, 64%) did not carry rare variants in any of the three genes. Biallelic and monoallelic IL36RN mutations were identified in 15 and five patients with GPP, respectively. Noncoding rare IL36RN variants were not identified in heterozygous carriers. The only significant genotype-phenotype correlation observed for IL36RN mutation carriers was early age at disease onset. Additional rare CARD14 or AP1S3 variants were identified in 15% of IL36RN mutation carriers. CONCLUSIONS: The identification of IL36RN mutation carriers harbouring additional rare variants in CARD14 or AP1S3 indicates a more complex mode of inheritance of pustular psoriasis. Our results suggest that, in heterozygous IL36RN mutation carriers, there are additional disease-causing genetic factors outside IL36RN.

Propranolol in the treatment of infantile haemangiomas: lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey.

BACKGROUND: Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres. OBJECTIVES: The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs. METHODS: Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool. RESULTS: The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg(-1) per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg(-1) vs. 2 mg kg(-1) vs. > 2 mg kg(-1) , the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33-1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04-5·46, P = 0·04, Ptrend < 0·001. CONCLUSIONS: The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.

[Medication-based therapy of infantile hemangioma and lymphatic malformations]. / Medikamentöse Behandlungsansätze für infantile Hämangiome und lymphatische Malformationen.

The therapy of vascular tumors and malformations should be interdisciplinary and performed according to available guidelines. Infantile hemangiomas (IH) are the most frequent vascular tumors of childhood and do not require treatment in most cases. If the IH is complicated by its location (e.g. facial or genital) or if the lesion threatens to cause loss of function, small localized IH should be treated by laser- or cryotherapy. If the IH is diffuse or rapidly growing it can be successfully treated using the ß blocker propranolol. The mechanism underlying the efficacy of this medication-based therapy is not completely understood and this still represents an experimental therapy. The results of molecular studies on vascular malformations have indicated new strategies for medical therapies. However, lymphatic malformations (LM) are still treated by surgery where possible, or sclerotherapy. Further investigations are necessary to determine whether new drugs such as the mTOR inhibitor rapamycin may be effective for treatment of diffuse LM. First case reports seem to be promising.

Successful treatment of ulcerated haemangioma with propranolol.

BACKGROUND: Ulceration is a frequent complication of proliferating haemangioma. METHODS: Four patients with ulcerated hemangioma aged 2, 4, 5 months and 5 weeks were treated with 2 mg/kg KG propranolol. RESULTS: Efficacy and safety of propranolol were excellent in all four cases. CONCLUSIONS: Propranolol may be the first-choice therapy for ulcerated haemangioma.

Prevalence of cerebral microhemorrhages in amateur boxers as detected by 3T MR imaging.

BACKGROUND AND PURPOSE: The evidence for traumatic brain injury in amateur boxers is controversial. Hypothetically, sudden acceleration of the head due to the impact of the blow during the boxing fight might result in diffuse axonal injury or contusion. We wanted to determine whether cerebral microhemorrhages occur more often in amateur boxers than in nonboxers. MATERIALS AND METHODS: In 42 male, classical amateur boxers and in 37 healthy, nonboxing male volunteers we performed cranial MR imaging at 3T. The study protocol included a transverse dual spin-echo MR imaging sequence, a 3D sagittal magnetization-prepared rapid acquisition of gradient echo sequence, a coronal T2*-weighted sequence, and an axial time-of-flight MR angiography sequence. MR imaging data were made anonymous before 2 neuroradiologists independently evaluated the images. In addition, the following risk factors were assessed: total numbers of fights and knockouts, weight division, and duration of boxing. We compared the group proportions of microhemorrhages with Fisher test of exact probability. RESULTS: There was a statistically higher prevalence of cerebral microhemorrhages in the group of boxers (3 of 42; 7.1%) than in nonboxing persons (0 of 37; 0%). This difference was not statistically significant, however (P = .2479; Fisher exact test). CONCLUSION: Although we detected more microhemorrhages in amateur boxers than in nonboxing persons, this difference did not prove to be significant.

Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling.

AIMS/HYPOTHESIS: Polycystic ovary syndrome (PCOS) is a risk factor of type 2 diabetes. Screening for impaired glucose metabolism (IGM) with an OGTT has been recommended, but this is relatively time-consuming and inconvenient. Thus, a strategy that could minimise the need for an OGTT would be beneficial. MATERIALS AND METHODS: Consecutive PCOS patients (n=118) with fasting glucose <6.1 mmol/l were included in the study. Parameters derived from medical history, clinical examination and fasting blood samples were assessed by decision tree modelling for their ability to discriminate women with IGM (2-h OGTT value >/=7.8 mmol/l) from those with NGT. RESULTS: According to the OGTT results, 93 PCOS women had NGT and 25 had IGM. The best decision tree consisted of HOMA-IR, the proinsulin:insulin ratio, proinsulin, 17-OH progesterone and the ratio of luteinising hormone:follicle-stimulating hormone. This tree identified 69 women with NGT. The remaining 49 women included all women with IGM (100% sensitivity, 74% specificity to detect IGM). Pruning this tree to three levels still identified 53 women with NGT (100% sensitivity, 57% specificity to detect IGM). Restricting the data matrix used for tree modelling to medical history and clinical parameters produced a tree using BMI, waist circumference and WHR. Pruning this tree to two levels separated 27 women with NGT (100% sensitivity, 29% specificity to detect IGM). The validity of both trees was tested by a leave-10%-out cross-validation. CONCLUSIONS/INTERPRETATION: Decision trees are useful tools for separating PCOS women with NGT from those with IGM. They can be used for stratifying the metabolic screening of PCOS women, whereby the number of OGTTs can be markedly reduced.

Use of GnRH antagonists in the treatment of endometriosis.

Endometriosis is an oestrogen-dependent disease that is treatable by oestrogen withdrawal, a therapy that has been effectively provided by the use of a gonadotrophin-releasing hormone (GnRH) agonist. Complete oestrogen withdrawal results in unacceptable side-effects, in particular in accelerated bone density loss. This problem has been effectively overcome with 'add-back therapy' using low-dose oestrogens and progestins in combination with a GnRH agonist to limit these side-effects, while still allowing regression of endometriotic lesions. The aim of this study was to determine the feasibility of using a subcutaneous injection of GnRH antagonist in the treatment of endometriosis. All patients (15/15; 100%) reported a symptom-free period during GnRH antagonist treatment, including mood changes, hot flushes, loss of libido, vaginal dryness and other symptoms. Serum oestradiol oscillated around a mean concentration of 50 pg/ml during therapy. Diagnostic laparoscopy before GnRH antagonist administration showed a mean stage III of disease. Regression occurred in 60% of cases (9/15) and the degree of endometriosis declined to stage II. Sequential administration of the GnRH antagonist cetrorelix (Cetrotide) in a 3 mg dosage once weekly over 8 weeks creates a new opportunity for medical treatment of symptomatic endometriosis. Preserving basic oestrogen production during the course of treatment apparently does not influence regression of disease, and has no major side-effects.

Use of frozen-thawed testicular sperm for intracytoplasmic sperm injection.

OBJECTIVE: To determine the feasibility of using frozen-thawed testicular spermatozoa for intracytoplasmic sperm injection. DESIGN: Prospective clinical study. SETTING: A university hospital. PATIENT(S): One hundred seventy-five azoospermic men participating in a routine intracytoplasmic sperm injection program. INTERVENTION(S): The men underwent testicular biopsy for cryopreservation of tissue to be used in consecutive intracytoplasmic sperm injection treatment cycles. Their female partners underwent controlled ovarian hyperstimulation for conventional IVF treatment. MAIN OUTCOME MEASURE(S): Fertilization and pregnancy rates. RESULT(S): In 77% of the patients, spermatozoa could be harvested from the testis by an open testicular biopsy technique and used for intracytoplasmic sperm injection after freezing and thawing of testicular tissue. Histopathologic evaluation revealed a Sertoli cell-only pattern in 21%, maturation arrest in 60%, and hypospermatogenesis in 19% of the patients. In 2. 9% of the patients, carcinoma in situ or a germ cell tumor was detected. In all patients, viable spermatozoa could be visualized after the tissue samples were thawed. One hundred thirty-five intracytoplasmic sperm injection treatment cycles were performed, with a fertilization rate of 45% and a clinical pregnancy rate of 30% per oocyte retrieved. CONCLUSION(S): The use of frozen-thawed testicular tissue allows ovarian stimulation of the female partner to be timed and avoids cancellation of ovum pick-up when spermatozoa cannot be retrieved.

Transcervical falloscopic dilatation of proximal tubal occlusion. Is there an indication?

Proximal tubal occlusion (PTO), until recently a domain of microsurgery, can also be treated by a transcervical balloon dilatation and/or tubal recanalization. The aim of our study was to evaluate the possibility of transcervical tubal dilatation during transcervical Falloposcopy. Transcervical Falloposcopy and tubal dilatation was performed under laparoscopic control. During a period of 48 months a total of 157 Falloposcopies was performed. Out of a total of 157 patients, 42 patients had PTO confirmed by dye-pertubation during laparoscopy. All patients were referred because of primary or secondary tubal infertility. A total of 18 patients had bilateral PTO by dye-pertubation and of these six patients had successful bilateral and seven patients successful unilateral recanalization. The remaining five patients were unable to recanalize. A total of 24 patients had an unilateral PTO by dye-pertubation, 13 of these patients had a contralateral diseased tube, seven of which could be recanalized. Four patients had contralateral normal tubes, with successful recanalization in one patient. Seven patients had an occluded or missing contralateral tube, five of which could be recanalized. A total of 60 tubes with PTO were diagnosed, of which 32 (53.3%) tubes could be recanalized. 20 of these had normal tubes. Only patients with healthy Fallopian tubes carried pregnancies to term (five pregnancies, 12% of all patients). All patients conceived within a period of 3-6 months. We observed no ectopic pregnancy.

A validity study of the MMPI-TRI Acting-out Scale.

49 college men and 45 women were administered the 1995 MMPI-TRI by Swanson, Templer, Thomas-Dobson, Cannon, Streiner, Reynolds, and Miller and a short form of the MMPI with scales for Subjective Distress, Acting-out, and Psychosis. To test the validity of the Acting-out scale respondents also took measures of sexual and aggressive acting out as well as a measure of alcohol use. They were asked about their use of drugs. Women had significant correlations between scores on the Acting-out Scale and scores on measures of Sexual Sensation Seeking .57, Sexual Compulsion .54, Anger Control -.40, Anger-out .50, Anger-in .32, and Drug Use .40. Men had significant correlations for scores on measures of Sexual Compulsion .51, Anger Control -.39, Anger-in .37, and Alcohol Use .35 but not Anger-out. Results suggest the Acting-out scale is more valid for college women than for men.

Relationships between Schill's Self-defeating Personality Scale and Coolidge's Personality Disorders Inventory.

81 men and 82 women were administered Schill's (1990) Self-defeating Personality Scale and Coolidge's (1992) Axis Two Inventory. As expected, Schill's and Coolidge's measures of self-defeating personality disorder were highly correlated (.70 for men and .74 for women). Scores on Schill's scale also had correlations > .50 with scores on six of the other personality disorder scales for men and five for women. This argues against self-defeating personality disorder as measured by Schill's scale being a distinct construct. The pattern of the correlations suggests that besides assessing a person's maladaptive self-defeating traits, Schill's measure also may assess the person's anxiety and concerns about interpersonal relationships.

Are childhood misbehavior and physical illness factors in the development of self-defeating personality.

49 undergraduate men and 45 women took Schill's 1990 Self-defeating Personality Scale and answered questions about their physical health and misbehavior as children and the amount of attention such behavior elicited from their parents. No support was found for the idea that individuals who currently score more self-defeating had been more likely to engage in such behavior or had been able to gain attention thereby. In fact, these people reported getting less rather than more attention from parents when they were physically ill. Results were discussed as consistent with prior findings wherein self-defeating individuals have described their parents as being nonsupportive, inconsistent, and rejecting.

Self-defeating personality, argumentativeness, and assertive self-statements.

55 men and 55 women were administered Schill's Self-defeating Personality Scale, an argumentativeness scale, and a measure of assertive self-statements. Women with higher scores on the Self-defeating Personality Scale had lower scores on the argumentativeness scale. Both men and women scoring higher on the Self-defeating Personality Scale recalled having thoughts which inhibited them from making assertive statements. These results were discussed as supporting prior research showing that persons reporting more self-defeating characteristics were relatively unassertive.

Relation of reports of sexual abuse to scores on Self Defeating Personality Scale.

One of the suggested antecedents of a pattern of self-defeating behavior has been the experience of sexual abuse. In this study 146 male and 129 female college students self-reported whether they had experienced sexual abuse using Russell's 1983) Sexual Abuse Interview Schedule. Thirty-nine men and 73 women self reported in the affirmative. For both men and women, the abused groups had significantly higher scores on Schill's 1990 Self-defeating Personality Scale. Results were related to other research, e.g., Kisler and Schill's 1995 work which showed scores on the Self-defeating scale were also correlated with scores on measures of bulimia and dissociative experiences.

Successful combination of transrectal electroejaculation and intracytoplasmic sperm injection in the treatment of anejaculation.

We describe the case of a couple whose infertility was caused by the absence of seminal emission following retroperitoneal surgery for testicular cancer. Ejaculate could be retrieved from the husband by rectal probe electroejaculation (RPE) but sperm quality was so poor that conventional in-vitro fertilization was impossible. With intracytoplasmic sperm injection of spermatozoa retrieved by RPE - a combination not reported previously - we were able to induce a pregnancy with successful outcome.

Hormone profiles under ovarian stimulation with human menopausal gonadotropin (hMG) and concomitant administration of the gonadotropin releasing hormone (GnRH)-antagonist Cetrorelix at different dosages.

PURPOSE: The premature LH surge in ART programs seems to be avoided by daily administration of the GnRH-antagonist Cetrorelix during the midcycle phase in controlled ovarian hyperstimulation with hMG. The dosage necessary for sufficient suppression of the pituitary gland is not yet defined. METHODS: To elucidate this question three daily dosages (3, 1, 0.5 mg) were administered and the hormone profiles obtained as well as the number of oocytes retrieved, the fertilization rate, and the consumption of HMG were compared. RESULTS: No premature LH surge could be observed at any of the three dosages administered. Both gonadotropins were deeply suppressed. The fertilization rates of the oocytes obtained were 45.3% in the 3-mg group, 53.1% in the 1-mg group, and 67.7% in the 0.5-mg group. The average uses of hMG ampoules were 30 in the 3-mg group, 27 in the 1-mg group, and 26 in the 0.5-mg group. CONCLUSIONS: Cetrolix, 0.5 mg/day, administered during the midcycle phase of controlled ovarian hyperstimulation with hMG is enough to prevent completely the premature LH surge. Perhaps even lower dosages would be sufficient. Regarding fertilization rates and use of hMG, the lower dosage seems to be the most favorable.

Social skills of persons with self-defeating personality.

55 undergraduate men and 55 women took Schill's 1990 Self-defeating Personality Scale and Lorr, Youniss, and Stefic's (1991) multidimensional Social Relations Survey. As expected, persons who endorsed more self-defeating characteristics scored lower on scales which make up the Social Skills or Assertiveness Factor. However, these scores did not have significant correlations with the Empathy or Social Approval Need Scales; two of the three scales which make up the Empathy Factor. The results were discussed in terms of prior work relating deficits in social skills to dysfunctional early parenting.

Morphology in intracytoplasmic sperm injection: preliminary results.

PURPOSE: Direct intracytoplasmic sperm injection (ICSI) is a successful treatment of severe male subfertility. Conventional in vitro fertilization shows poor pregnancy rates especially in cases of severe teratozoospermia. The objective was to determine if severe morphological defects of spermatozoa in oligoasthenoteratozoospermia (OAT) have any impact on the fertilization process in ICSI and if there are any specific morphological characteristics in nonfertilized oocytes after the ICSI procedure. METHODS: Ejaculates and nonfertilized oocytes were investigated by electron microscopy. CONCLUSIONS: The lack of intracytoplasmic sperm-oocyte interaction, not severe sperm defects, displays the most critical role in the fertilization process. Clinical data with fertilization rates of 66% and pregnancy rates of 23.3% confirm the fertilization capacity of severely