Evaluation of rheumatoid arthritis and connective tissue disease-related interstitial lung disease with pulmonary physiologic test,HRCT, and patient-based measures of dyspnea and functional disability

Objectives

We aim to investigate the relationship between pulmonary function and imaging parameters with symptom-related patient-reported outcome measures (PROs).

Method

We included 65 patients of rheumatoid arthritis (RA) and connective tissue disease (CTD) with and without interstitial lung disease (ILD) into this cross-sectional study. We evaluated the relationship between FVC, DLco, and PROs and compared to HRCT findings. PROs included visual analogue scale for breathing, modified Borg scale, medical research council dyspnea scale, St. George’s respiratory questionnaire (SGRQ), Leicester cough questionnaire, and Short Form 36 quality of life (SF-36 QoL).

Results

The mean age was 57.4 ± 9.7 and 61.9% (39/65) of patients had an established ILD. In RA-ILD group, SGRQ score was higher (p < 0.001) and SF-36 physical functioning score was lower (p = 0.02) than CTD-ILD group. In RA group, there was a significant correlation between FVC and SF-36 role functioning/physical score (r = 0.724, p = 0.012). In CTD group, SF-36 general health score was correlated with both FVC (r = 0.441, p = 0.045) and DLco (r = 0.485, p = 0.035), and also SF-36 physical functioning score was correlated with FVC (r = 0.441, p = 0.040). PROs were found to be similar between ILD and non-ILD patients. SF-36 QoL total and SGRQ outcomes were worse in non-ILD group.

Conclusions

We concluded that PROs could be used to evaluate health-related quality of life (HRQoL) in RA- or CTD-related ILD. The physical health determinants of HRQoL are measurably worse in RA-ILD patients than in CTD patients. But, PROs may not be very helpful in differentiating patients with cough and/or shortness of breath due to ILD or non-ILD causes in RA/CTD.

Key points

? HRQoL may be affected differently among specific subtypes of ILD.

? PROs can be used to evaluate dyspnea and function of patients with RA- or CTD-related ILD but are not distinguished from patients with cough and/or shortness of breath due to non-ILD causes in RA/CTD.

     

Efficacy and safety of the direct renin inhibitor aliskiren and ramipril alone or in combination in patients with diabetes and hypertension.

OBJECTIVE: To assess the antihypertensive efficacy and safety of the combination of the direct renin inhibitor aliskiren and ramipril in patients with diabetes and hypertension. METHODS: In this double-blind, multicentre trial, 837 patients with diabetes mellitus and hypertension (mean sitting diastolic blood pressure [BP] > 95 and < 110 mmHg) were randomised to once-daily aliskiren (150 mg titrated to 300 mg after four weeks; n=282), ramipril (5 mg titrated to 10 mg; n=278) or the combination (n=277) for eight weeks. Efficacy variables were cuff mean sitting diastolic BP (msDBP) and mean sitting systolic BP (msSBP); 24-hour ambulatory BP, plasma renin activity (PRA) and plasma renin concentration (PRC) were also assessed. RESULTS: At week 8, aliskiren, ramipril and aliskiren/ramipril lowered msDBP (mean+/-SEM) by 11.3+/-0.5, 10.7+/-0.5 and 12.8+/-0.5 mmHg, and msSBP by 14.7+/-0.9, 12.0+/-0.9 and 16.6+/-0.9 mmHg, respectively. Aliskiren/ramipril provided superior msDBP reductions to ramipril (p=0.004) or aliskiren (p=0.043) monotherapy; adding aliskiren to ramipril provided an additional mean BP reduction of 4.6/2.1 mmHg. Aliskiren monotherapy was non-inferior to ramipril for msDBP reduction (p=0.0002) and superior for msSBP reduction (p=0.021). All treatments significantly lowered mean 24-hour ambulatory BP. Aliskiren significantly reduced PRA from baseline as monotherapy (by 66%, p<0.0001) or in combination with ramipril (by 48%, p<0.0001), despite large increases in PRC in all treatment groups. Aliskiren was well tolerated as monotherapy or in combination with ramipril. CONCLUSIONS: Combining aliskiren with ramipril provided a greater reduction in msDBP than either drug alone in patients with diabetes and hypertension.     

Alternobaric vertigo in sport SCUBA divers and the risk factors

We investigated the eustachian tube function and the incidence of alternobaric vertigo (AV) in 29 sport self-contained underwater breathing apparatus (SCUBA) divers with, or without, some possible risk factors for AV. The divers had normal audiological and otoscopic findings at the pre-dive examination. We used the nine-step inflation/deflation tympanometric test and Toynbee test for evaluation of eustachian tube function, and the Valsalva manoeuvre for patency. Information on divers, their history, and their otolaryngologic examination were obtained in the pre-dive examination. Divers performed 1086 dives (mean 37, range: 3-100) during the observation period. Four divers (14 per cent) experienced AV during five dives (0.46 per cent), (one diver experienced AV two times). It was found that having an otitis media history or eustachian tube dysfunction determined with the nine-step inflation/deflation tympanometric test before diving, or difficulty in clearing ears during diving could be important risk factors for AV in sport SCUBA divers (p <.05). Divers with such findings seem to be more prone to AV and should pay rigorous attention to the precautions for prevention of AV.     

Influence of anaesthetic agents on transient evoked otoacoustic emissions and stapedius reflex thresholds

This aim of this study was to determine the effect of anaesthetic agents on stapedius reflex (SR) thresholds and transient evoked otoacoustic emissions (TEOAE). Fifty patients who were scheduled for operation and who had normal hearing were included in the study. All were given midazolam for premedication and propofol for induction. Anaesthesia was maintained in five different ways in each group of 10 patients. Groups I-IV received inhalational anaesthesia: group I received 70 per cent N2O plus 30 per cent O2, group II sevoflurane, group III desflurane and group IV halothane. Group V received total intravenous anaesthesia with propofol plus sufentanil. The SR and TEOAE of the patients were measured four times: on the day before surgery (first measurement), after premedication (second measurement), after induction of anaesthesia (third measurement) and during maintenance of anaesthesia (fourth measurement). Midazolam significantly increased ipsilateral and contralateral SR thresholds and decreased TEOAE wave reproducibility. Propofol significantly increased only the SR thresholds. The other anaesthetic agents significantly increased only the contralateral reflex thresholds. Of these, the highest increase was seen after sevoflurane and the lowest after halothane. The changes in TEOAE wave reproducibility due to anaesthetic agents used for maintenance were not significant. We concluded that midazolam premedication may affect audiological evaluation with SR and TEOAE tests, and sevoflurane should not be used when it is necessary to measure SR under general anaesthesia.     

Otoacoustic emissions in young adults with a history of otitis media

The aim of this study was to investigate otoacoustic emissions in young adults who had a history of otitis media (OM) in childhood and to assess whether a history of OM had an irreversible effect on hearing. We studied 116 cases between 15 and 25 years of age, divided into three groups. Each subject underwent a single examination comprising otoscopy, pure-tone audiometry (PTA), tympanometry, and transient evoked otoacoustic emission (TEOAE) and distortion product otoacoustic emission (DPOAE) testing. Subjects in the first and second groups had normal audiometric hearing thresholds and type A tympanograms. The only difference between the first and second group was the presence or absence of a history of OM. The third group consisted of patients diagnosed as having active OM; these patients had poorer hearing thresholds and type B or C tympanograms. After statistical analysis of TEOAE and DPOAE results (one-way analysis of variance test), significant differences were noted between groups. Otoacoustic emission levels were, unsurprisingly, lowest in the third group, as expected. However, the most striking result in the study was that significantly fewer otoacoustic emissions were detected in subjects with a history of OM than in subjects without a history of OM. These findings suggest that OM in childhood may cause minor but irreversible damage to the middle ear or cochlea. Otoacoustic emissions testing can be used to detect this sub-clinical damage.     

Impact of transrectal prostate needle biopsy on erectile function: Results of power Doppler ultrasonography of the prostate

We evaluated the impact of transrectal prostate needle biopsy (TPNB) on erectile function and on the prostate and bilateral neurovascular bundles using power Doppler ultrasonography imaging of the prostate. The study consisted of 42 patients who had undergone TPNB. Erectile function was evaluated prior to the biopsy, and in the 3rd month after the biopsy using the first five-item version of the International Index of Erectile Function (IIEF-5). Prior to and 3 months after the biopsy, the resistivity index of the prostate parenchyma and both neurovascular bundles was measured. The mean age of the men was 64.2 (47–78) years. Prior to TPNB, 10 (23.8%) patients did not have erectile dysfunction (ED) and 32 (76.2%) patients had ED. The mean IIEF-5 score was 20.8 (range: 2–25) prior to the biopsies, and the mean IIEF-5 score was 17.4 (range: 5–25; p < 0.001) after 3 months. For patients who were previously potent in the pre-biopsy period, the ED rate was 40% (n = 4/10) at the 3rd month evaluation. In these patients, all the resistivity index values were significantly decreased. Our results showed that TPNB may lead to an increased risk of ED. The presence of ED in men after TPNB might have an organic basis.     

Dermoid cyst of the parotid gland: First pediatric case

A dermoid cyst is the result of inclusion of epithelial cells along the lines of embryonic closure. Dermoid cysts of the head neck are uncommon and account for only 7% of all such cysts. They are most often reported as arising in the floor of the mouth. Dermoid cyst is rarely seen in the parotid gland. To our knowledge, there have been only six previous case reports in the English literature. Dermoid cyst of the parotid gland in pediatric patient has not been previously reported in the literature. This is the first case report concerning a dermoid cyst in a pediatric patient.     

ECTO-NOX target for the anticancer isoflavene phenoxodiol

Phenoxodiol, a synthetic isoflavene with clinical efficacy in the management of ovarian and other forms of human cancer, blocked the activity of a cancer-specific and growth-related cell surface ECTO-NOX protein with both oxidative (hydroquinone) and protein disulfide-thiol interchange activity designated tNOX. Purified recombinant tNOX bound phenoxodiol with high affinity (Kd of 50 nM). The tNOX protein appeared to be both necessary and sufficient for the cancer-specific cytotoxicity of phenoxodiol. Growth inhibition of fibroblasts from embryos of mice expressing a tNOX transgene, but not from wild-type mice, was inhibited by phenoxodiol followed by apoptosis. Both the oxidative and protein disulfide-thiol interchange activities that alternate to generate the complex set of oscillations with a period length of 22 min (24 min for the constitutive counterpart CNOX) that characterize ECTO-NOX proteins respond to phenoxodiol. Oxidation of NADH or reduced coenzyme Q10 was rapidly blocked by phenoxodiol. In contrast, the protein disulfidethiol interchange activity measured either by the restoration of activity to scrambled and inactive RNase or from the cleavage of dithiodipyridine (EC50 of 50 nM) was inhibited progressively over an interval of 60 min that spanned three cycles of activity. Inhibition of the latter paralleled the inhibition of cell enlargement and the consequent inability of inhibited cells to initiate traverse of the cell cycle. Activities of constitutive ECTO-NOX (CNOX) forms of either cancer or noncancer cells were unaffected by phenoxodiol to help explain how the cytotoxic effects of phenoxodiol may be restricted to cancer cells.     

B Cells Are Critical to T-cell-Mediated Antitumor Immunity Induced by a Combined Immune-Stimulatory/Conditionally Cytotoxic Therapy for Glioblastoma

We have demonstrated that modifying the tumor microenvironment through intratumoral administration of adenoviral vectors (Ad) encoding the conditional cytotoxic molecule, i.e., HSV1-TK and the immune-stimulatory cytokine, i.e., fms-like tyrosine kinase 3 ligand (Flt3L) leads to T-cell-dependent tumor regression in rodent models of glioblastoma. We investigated the role of B cells during immune-mediated glioblastoma multiforme regression. Although treatment with Ad-TK+Ad-Flt3L induced tumor regression in 60% of wild-type (WT) mice, it completely failed in B-cell-deficient Igh6^-/- mice. Tumor-specific T-cell precursors were detected in Ad-TK+Ad-Flt3L-treated WT mice but not in Igh6^-/- mice. The treatment also failed in WT mice depleted of total B cells or marginal zone B cells. Because we could not detect circulating antibodies against tumor cells and the treatment was equally efficient in WT mice and in mice with B-cell-specific deletion of Prdm 1 (encoding Blimp-1), in which B cells are present but unable to fully differentiate into antibody-secreting plasma cells, tumor regression in this model is not dependent on B cells'' production of tumor antigen-specific immunoglobulins. Instead, B cells seem to play a role as antigen-presenting cells (APCs). Treatment with Ad-TK+Ad-Flt3L led to an increase in the number of B cells in the cervical lymph nodes, which stimulated the proliferation of syngeneic T cells and induced clonal expansion of antitumor T cells. Our data show that B cells act as APCs, playing a critical role in clonal expansion of tumor antigen-specific T cells and brain tumor regression.