20q13.2 Amplification in intraductal hyperplasia adjacent to in situ and invasive ductal carcinoma of the breast

The 20q13 region harboring recently described putative oncogenes is frequently amplified in invasive ductal carcinoma (IDC). The aim of this study was to examine the 20q13 copy number in intraduct hyperplasia (IH), atypical duct hyperplasia (ADH), and ductal carcinoma in situ (DCIS) adjacent to IDC. In 5 patients, comparative genomic hybridization (CGH) after laser microdissection revealed 20q13 amplification in four of five cases of IH, in all of three cases of IH with atypia, all five of DCIS, and all five of IDC. Fluorescence in situ hybridization (FISH) confirmed the amplification at 20q13.2 in IH in the two specimens analyzed. The amplification rate, however, was higher in DCIS and IDC. In phenotypically normal ductal epithelium normal values were found for 20q13 copy number by FISH (n=2) and CGH (n=5). Although the number of cases presented here is small, our results suggest that mutations in the 20q13.2 region in IH may be associated with accelerated proliferation and hyperplasia of the ductal epithelium. Progression to DCIS and ICD is accompanied by a further increase in the 20q13.2 copy number. Received: 17 March 1999 / Accepted: 22 June 1999     

Subgroups in the treatment of nasal polyposis with dupilumab: A retrospective study

Dupilumab has been shown to be safe and effective in treating chronic rhinosinusitis with polyposis (CRSwNP). There is to this date no published data whether subgroups like patients with aspirin exacerbated respiratory disease (AERD), increased histologic eosinophilia or elevated blood eosinophil or IgE-levels benefit greater from dupilumab therapy. Moreover, there is no data comparing the efficacy of functional endoscopic sinus surgery (FESS) with dupilumab therapy. We conducted a retrospective chart review of all patients that were treated at a tertiary referral center for CRswNP with dupilumab. We also contacted the patients with a questionnaire to evaluate the efficacy of previous surgeries and dupilumab therapy by visual analogue scale (VAS) and the glasgow benefit inventory (GBI) as well as report on side effects. Overall, 75 patients were included in the study at hand that reported back 138 times. While dupilumab treatment was efficient, we found no systematic evidence of greater efficacy of dupilumab in patients with AERD, histologic eosinophilia or increased blood eosinophil or IgE-levels. All patients showed a considerable decrease in subjective burden of disease, objective smell tests and endoscopic findings. From the patients point of view, dupilumab therapy showed greater efficacy both in the VAS and the GBI overall and all subcategories but “social support.” Dupilumab is efficient in treating CRSwNP; this effect is independent from disease characteristics like AERD, histologic eosinophilia, serum IgE-levels or eosinophil counts. There seems to be a group of patients that benefit greater from dupilumab therapy compared to FESS.     

Insomnia and circadian variation of attacks in episodic migraine

OBJECTIVES: To assess the influence of insomnia on the 24-hour temporal pattern of migraine. BACKGROUND: Migraine attacks have been reported to occur in a harmonic (monophasic) or a biphasic 24-hour cyclic manner, and in some studies to have preponderance in the morning hours. The influence of insomnia on the circadian pattern has not been evaluated. METHOD: Based on a previous study of the circadian variation in migraine, an explorative data analysis was made to compare the circadian pattern of insomnia-related migraine attacks to the circadian pattern of migraine attacks not related to insomnia. If the patients reported difficulties in falling asleep and/or maintaining sleep the night prior to the reported attack or the night the attack occurred, the attack was defined as insomnia-related. Relapses were not counted as distinctive attacks. RESULTS: Sixty-eight female migraineurs (mean +/- SD age: 35.5 +/- 7.0) prospectively recorded 1869 migraine attacks. Five hundred-and-thirty-three attacks (29%) were insomnia-related. Insomnia-related attacks had a biphasic temporal pattern with one peak in the morning hours and one peak after noon. They had a preponderance in the morning hours compared to attacks not related to insomnia (t= 3.27, df = 62, P= .002). In 79% of attacks insomnia was experienced prior to the headache. CONCLUSIONS: Episodic morning migraine is associated with insomnia. The cause and consequences of insomnia in migraine is not clarified, but sleep obviously protects against attacks rather than provokes them.     

Head injury and the Satz-Mogel type short form WAIS-R

The current study investigated the efficacy of a Satz-Mogel type short form of the WAIS-R in a closed head injury (CHI) population and whether the short form's effectiveness varied by lesion site. Data were taken from the files of 79 CHI patients, 20 with left hemisphere damage, 15 with right hemisphere damage, 29 with bilateral damage, and 15 with only diffuse damage. Information about IQ scores and age-corrected subtest scores was examined. As expected, correlations between two forms, for both IQ scores and subtest scores were high. However, there was a remarkable percentage of deviation in scaled score points and changes in intellectual classification for some of these scores. No evidence was found to support the notion that usefulness of the short form varied according to the location of lesion.     

Sarcoidosis of the paranasal sinuses

European Archives of Oto-Rhino-Laryngology - Sarcoidosis is a chronic disease, which predominantly affects the lung. Since sinonasal sarcoidosis is rare, little is known about the sarcoidosis...     

Evaluation of referrals from general practice to a neurological department

BACKGROUND: The presence of neurological deficits as obtained from clinical examination increases the likelihood of detecting serious underlying brain disorders. OBJECTIVES: In this study, we assessed the frequency of reported clinical neurological examination in patients referred to neurology. METHODS: We consecutively evaluated referrals to a neurological centre during a 6-month period. RESULTS: From a total of 716 patients, 377 (51%) had an examination reported in the referral letter. Clinical examinations were reported more often in patients with musculo-skeletal disorders compared with others, P = 0.0001. Examination was less likely to be reported in those with a history of disturbed consciousness. CONCLUSION: By showing that only about half of the patients had an examination reported, the study demonstrates that the process of selecting those with a high priority for a secondary neurological service can be improved.     

In vitro growth and stability of recombinant rabies viruses designed for vaccination of wildlife

Three live rabies virus (RV) recombinant vaccine candidates, SPBNGA, SPBNGA-Cyto c (+), and SPBNGA-GA, were examined for their production levels and stability. Maximum production levels up to 10(10) infectious particles/mL were achieved using bioreactor technology. All virus lots exhibited thermostability profiles typical for RV vaccines and were non-pathogenic for intracranially inoculated immunocompetent mice. Moreover, sequence analysis indicated high genetic stability in all three RVs during 10 consecutive passages in newborn mice. This analysis revealed no change in the extra RV G gene in the SPBNGA-GA vaccine or in the cytochrome c gene in the SPBNGA-Cyto c (+) vaccine. Moreover, no changes were detected in the G gene codon for Glu333, which renders the virus non-pathogenic. However, after the fifth passage, a mutation resulting in an Asn194 --> Lys194 exchange emerged in the G genes of all three RVs. This mutation was associated with a modest increase in pathogenicity in SPBNGA and SPBNGA-Cyto c (+), but not in SPBNGA-GA, which contained the mutation in only one of its two G genes and which remained non-pathogenic. These results demonstrate the feasibility of producing RV vaccines that remain highly stable even after multiple passages.