Time-varying signal analysis to detect high-altitude periodic breathing in climbers ascending to extreme altitude.

This work investigates the performance of cardiorespiratory analysis detecting periodic breathing (PB) in chest wall recordings in mountaineers climbing to extreme altitude. The breathing patterns of 34 mountaineers were monitored unobtrusively by inductance plethysmography, ECG and pulse oximetry using a portable recorder during climbs at altitudes between 4497 and 7546 m on Mt. Muztagh Ata. The minute ventilation (VE) and heart rate (HR) signals were studied, to identify visually scored PB, applying time-varying spectral, coherence and entropy analysis. In 411 climbing periods, 30-120 min in duration, high values of mean power (MP(VE)) and slope (MSlope(VE)) of the modulation frequency band of VE, accurately identified PB, with an area under the ROC curve of 88 and 89%, respectively. Prolonged stay at altitude was associated with an increase in PB. During PB episodes, higher peak power of ventilatory (MP(VE)) and cardiac (MP(LF)(HR) ) oscillations and cardiorespiratory coherence (MP(LF)(Coher)), but reduced ventilation entropy (SampEn(VE)), was observed. Therefore, the characterization of cardiorespiratory dynamics by the analysis of VE and HR signals accurately identifies PB and effects of altitude acclimatization, providing promising tools for investigating physiologic effects of environmental exposures and diseases.

Treatment of traumatic corneal abrasions: a three-arm, prospective, randomized study.

PURPOSE: To compare three different treatment modalities for traumatic corneal abrasions. METHODS: We conducted a prospective, randomized, masked, three-arm clinical study of patients presenting with superficial corneal foreign bodies. Treatment modalities were: (1) pressure patching with ofloxacin ointment (patch group, PG, n = 18), (2) therapeutic contact lens with ofloxacin eye drops (contact lens group, CLG, n = 20) and (3) ofloxacin ointment alone (ointment group, OG, n = 28). Primary outcome measure was the difference of the mean corneal abrasion area between the three groups at 3 different time points (baseline, day 1 and day 7). RESULTS: A total of 66 patients were included in the study over a period of 2 years. Mean initial corneal abrasion area was 3.6 ± 3.4 mm² in the PG, 4.2 ± 4.0 mm² in the CLG and 3.7 ± 3.1 mm² in the OG (p = 0.875). Differences in corneal abrasion area at any time point were not statistically significant (abrasion area decrease from presentation to day 1 was 3.4 ± 3.3 mm² in the PG, 4.1 ± 4.0 mm² in the CLG and 3.5 ± 3.1 mm² in the OG, p = 0.789). The epithelium was healed in all patients at day 7. CONCLUSIONS: Treating traumatic corneal abrasions by pressure patching, a bandage contact lens or ointment alone was equal in reducing the abrasion area or reducing pain. According to our results the treatment of choice for traumatic abrasions may be adapted to the needs and preferences of the patient.

Acclimatization improves submaximal exercise economy at 5533 m.

We tested whether the better subjective exercise tolerance perceived by mountaineers after altitude acclimatization relates to enhanced exercise economy. Thirty-two mountaineers performed progressive bicycle exercise to exhaustion at 490 m and twice at 5533 m (days 6-7 and day 11), respectively, during an expedition to Mt. Muztagh Ata. Maximal work rate (W(max)) decreased from mean ± SD 356 ± 73 watts at 490 m to 191 ± 49 watts and 193 ± 45 watts at 5533 m, days 6-7 and day 11, respectively; corresponding maximal oxygen uptakes (VO2max ) were 50.7 ± 9.5, 26.3 ± 5.6, 24.7 ± 7.0 mL/min/kg (P = 0.0001 5533 m vs 490 m). On days 6-7 (5533 m), VO(2) at 75% W(max) (152 ± 37 watts) was 1.75 ± 0.45 L/min, oxygen saturation 68 ± 8%. On day 11 (5533 m), at the same submaximal work rate, VO(2) was lower (1.61 ± 0.47 L/min, P < 0.027) indicating improved net efficiency; oxygen saturation was higher (74 ± 7%, P < 0.0004) but ratios of VO(2) to work rate increments remained unchanged. On day 11, mountaineers climbed faster from 4497 m to 5533 m than on days 5-6 but perceived less effort (visual analog scale 50 ± 15 vs 57 ± 20, P = 0.006) and reduced symptoms of acute mountain sickness. We conclude that the better performance and subjective exercise tolerance after acclimatization were related to regression of acute mountain sickness and improved submaximal exercise economy because of lower metabolic demands for non-external work-performing functions.

Periodic breathing during ascent to extreme altitude quantified by spectral analysis of the respiratory volume signal.

High altitude periodic breathing (PB) shares some common pathophysiologic aspects with sleep apnea, Cheyne-Stokes respiration and PB in heart failure patients. Methods that allow quantifying instabilities of respiratory control provide valuable insights in physiologic mechanisms and help to identify therapeutic targets. Under the hypothesis that high altitude PB appears even during physical activity and can be identified in comparison to visual analysis in conditions of low SNR, this study aims to identify PB by characterizing the respiratory pattern through the respiratory volume signal. A number of spectral parameters are extracted from the power spectral density (PSD) of the volume signal, derived from respiratory inductive plethysmography and evaluated through a linear discriminant analysis. A dataset of 34 healthy mountaineers ascending to Mt. Muztagh Ata, China (7,546 m) visually labeled as PB and non periodic breathing (nPB) is analyzed. All climbing periods within all the ascents are considered (total climbing periods: 371 nPB and 40 PB). The best crossvalidated result classifying PB and nPB is obtained with Pm (power of the modulation frequency band) and R (ratio between modulation and respiration power) with an accuracy of 80.3% and area under the receiver operating characteristic curve of 84.5%. Comparing the subjects from 1(st) and 2(nd) ascents (at the same altitudes but the latter more acclimatized) the effect of acclimatization is evaluated. SaO(2) and periodic breathing cycles significantly increased with acclimatization (p-value < 0.05). Higher Pm and higher respiratory frequencies are observed at lower SaO(2), through a significant negative correlation (p-value < 0.01). Higher Pm is observed at climbing periods visually labeled as PB with > 5 periodic breathing cycles through a significant positive correlation (p-value < 0.01). Our data demonstrate that quantification of the respiratory volume signal using spectral analysis is suitable to identify effects of hypobaric hypoxia on control of breathing.

Fibrotic racemose haemangioma of the retina.

BACKGROUND: The racemose - or arteriovenous - haemangioma of the retina is a rare developmental anomaly. It can be associated with similar vascular anomalies in other regions of the central nervous system (Wyburn-Mason syndrome). HISTORY AND SIGNS: We report a 24-year-old woman with a chronic headache from our outpatient clinic. Other than a white tortuous strand in the retina of the right eye, which resembled a filarium at first glance, no pathologies were found. Its ends were located at the optic disc forming a sling-shaped lesion extending to the anterior nasal periphery. Partial filling was shown by fluorescence angiography. An MRI of the neurocranium detected no additional vascular abnormalities. THERAPY AND OUTCOME: So far our patient has not suffered from any visual complaints and she will be followed up yearly. CONCLUSIONS: We show an unusual presentation of a retinal racemose haemangioma. Diagnosis of this entity should prompt further examinations to exclude any additional haemangiomas with respect to the Wyburn-Mason syndrome.

[Photodynamic therapy of AMD for the first (better sight) and the second (worse sight) eyes]. / Photodynamische Therapie bei altersbedingter Makuladegeneration am schlechteren und besseren Auge.

BACKGROUND: Photodynamic therapy (PDT) is the standard treatment procedure for many forms of exudative and/or neovascular AMD. Despite therapy, visual acuity often drops to low vision levels. The cost efficiency of treating the eye in which vision is worse is therefore the subject of some controversy. PATIENTS AND METHODS: A retrospective case-control study was conducted in all patients who were treated with PDT at the Universitätsspital Zürich between September 1999 and November 2004. Each patient's first (with worse vision) and second (with better vision) eyes were compared for situation on presentation and course during treatment. RESULTS: In 117/228 cases (51.3%) visual acuity of the treated eye was better than (or identical to) that of the fellow eye at presentation. Visual acuity before therapy was an average of 0.58+/-0.27 logMAR [Snellen: 0.26 (0.14-0.49)] in the eyes with better visual acuity and 0.69+/-0.4 logMAR [Snellen 0.20 (0.08-0.51)] in the fellow eyes (p=0.015). After therapy there was no significant difference between the patient groups in visual acuity or in the magnitude of any change in visual acuity, or in lesion size or change in lesion size. CONCLUSION: The outcome of PDT of a second eye (with better visual acuity) is not significantly better than the result obtained in the first eye (the one with worse visual acuity initially).

Macular atrophy after combined intravitreal triamcinolone acetonide (IVTA) and photodynamic therapy (PDT) for retinal angiomatous proliferation (RAP).

BACKGROUND: Retinal angiomatous proliferation (RAP) is a variant of exudative AMD that appears to respond poorly to standard PDT. This pilot study explores the potential efficacy and safety of combined intravitreal triamcinolone acetonide (IVTA). PATIENTS AND METHODS: In a prospective interventional case series 10 eyes of 8 patients with RAP were treated with combined IVTA/PDT. RESULTS: After 3 months there was no evidence of significant exudative activity in 7/10 eyes treated with IVTA/PDT, three eyes required re-treatment. After 6 months 4/10 eyes were "dry" on fluorescein angiography, visual acuity was stable (loss of less than 3 Snellen lines) or had improved in 5/10 eyes. 5/10 eyes had lost 3 or more lines, due to central macular atrophy in 4/5 eyes and secondary to a progressive exudative lesion in 1/5 eyes. CONCLUSIONS: Intravitreal steroids combined with PDT appear to be a step ahead in the treatment of RAP. Our results, however, raise the question whether combined treatment may create more atrophy leading to vision loss in some cases.

Blackening of a choroidal hemangioma after photodynamic therapy.

BACKGROUND: Photodynamic therapy has recently advanced to a first line treatment of symptomatic circumscribed choroidal hemangiomas. HISTORY AND SIGNS: A sixty-year-old male patient was referred with progressive visual loss in his left eye. Visual acuity measured 20/80 and fundus examination revealed a prominent red subretinal lesion superior to the fovea with adjacent pigment epithelial irregularities. Thickening of the central retina was seen on OCT imaging. Sonography revealed a dome-shaped lesion with a maximal thickness of 3.3 mm and high internal reflectivity. Combined fundus indocyanine green and fluorescein angiography showed early filling of large vessels within the tumor. THERAPY AND OUTCOME: The hemangioma was treated with verteporphin photodynamic therapy. Two days after treatment, with vision unchanged, fundus examination revealed blackening of the tumor. Two months later vision increased to 20/40 and the tumor area was atrophic and bright red with a slight hyperpigmented rim. Angiography revealed the disappearance of tumor vessels and choroidal hypoperfusion in the area of treatment. CONCLUSIONS: Choroidal hemangiomas may darken initially after photodynamic therapy. This is most probably caused by large coaguli within the voluminous lacuna-like blood-filled vessel system of the hemangioma that are induced by photothrombosis.

Lessons from the experimental stage of the two-step vacuum-microwave method for histoprocessing.

The two-step vacuum-microwave method simplifies and shortens histoprocessing. Acting margins are small so that fine-tuning is required. Temperature, vacuum and time should be in perfect balance. If not, a "cooking" effect (too high temperature) can easily be detected in the epidermis of skin biopsies. An adverse vacuum effect (when vacuum is obtained too abruptly) produces clefts, first observed where different tissues are contiguous. When time is set too shortly, impregnation will be insufficient, which is best seen in kidney tissue. The lessons from these observations may help future users to be troubleshooters while installing their unit.

Proliferation profile of benign and premalignant cervical epithelium as established by PCNA staining pattern.

Since immunohistochemical detection of proliferating cell nuclear antigen (PCNA) is closely related to the cell cycle, this method can be used to visualize proliferative activity in paraffin sections of benign and premalignant cervical lesions. This was done in two types of benign lesions, immature and mature metaplasia, and the three types of CIN (I, II, and III). PCNA staining was assessed as heavy, faint, or negative nuclei in the deep, middle, and superficial layers of the epithelium. In the analysis of variance, significant differences between the three layers and between the five groups were found. The PCNA values can be helpful to distinguish immature metaplasia from CIN I. The values for PCNA-positive (heavy+faint) for an individual lesion at the three layers constitute its proliferation profile. The PCNA profiles of the CIN lesions differ fundamentally from the metaplasia profiles. It is conceivable that for an individual CIN lesion, PCNA staining might be prognostically more valuable than its CIN grade.

Profile of the malignant melanoma excised in general practice.

An analysis of 27 malignant melanomas diagnosed in a Dutch laboratory specializing in the provision of a cytology and pathology service to general practitioners is reported. The median age of the patients was 39 years, and was lower in women (30 years) than in men (54 years). In the national data the mean age was 52 years for both sexes. There were twice as many women as men. There were no tumours from the head and neck region. The ratio of tumours on the limbs to those on the trunk was 3:2. The melanomas were very small (74% with a diameter of < or = 6.0 mm), and they were also very thin (74% with a Breslow thickness < or = 1.0 mm), compared with the national data in which 62% were < or = 1.0 mm. Not surprisingly, the estimated mean 5-year survival was favourable (95% for women and 76% for men). After a period of follow-up ranging from 2 to 32 months, none of the patients had any evidence of residual disease. This study demonstrates that in skin biopsies performed by general practitioners melanomas are mainly detected by chance, and have a very good prognosis.

A comparative burn wound model in the New Yorkshire pig for the histopathological evaluation of local therapeutic regimens: silver sulfadiazine cream as a standard.

A standard burn wound model was developed in the pig to enable evaluation of histopathological parameters of wound healing under different circumstances. Wounds on one flank were treated with silver sulfadiazine 1% cream (SSD, Flammazine-Duphar), which is a standard treatment. On identical places of the contralateral side different topical agents were applied. From the SSD treated burns a typical histopathologic picture of wound healing under SSD could be derived: SSD has the potential to preserve viable dermal tissue, epidermal regeneration is rather slow and irritated, while the formation of granulation tissue is pronounced, with an abundance of myofibroblasts.

Characteristics of false-negative smears tested in the normal screening situation.

It is common practice to rescreen false-negative (FN) smears. However, it is inevitable that this is done with some foreknowledge; at least it is known that the test smears contain one or more special cases. Therefore, we decided to test smears in the normal screening situation, when cytotechnologists are completely unaware of being tested. This experiment was done with five FNs and five true-positive (TP) smears. In a third experiment the FNs were tested with the cytotechnologists aware of their presence. Finally, 10 qualities of FNs and TPs were analyzed. In the normal screening situation, only in 1 of 25 tests was the FN recognized as malignant, while all the TPs were detected at the first testing. However, when the cytotechnologists were aware of being tested, the FN was detected in seven of eight tests. The FNs differed from the TPs in 5 of the 10 analyzed characteristics. FNs contained few (if any) large neoplastic epithelial fragments. Detached malignant cells were nearly lacking. The cancer cells had small nuclei that presented little anisokaryosis. The FNs possessed generally hypochromatic nuclei. These features explain why the malignant cells were almost never identified in the normal screening situation. We conclude that FNs and TPs differ and that it seems virtually impossible to avoid all false-negative diagnoses.

Fine-needle cytology of an eccrine spiradenoma of the breast: diagnosis made by a holistic approach.

Eccrine spiradenoma is a rather rare adnexal tumor of the skin. When the clinical presentation is that of a breast neoplasm, diagnosis can be difficult. As cytology was a new procedure for this tumor, the approach of choice appeared to be a holistic one. The cytologic picture showed bland groups of uniformly sized cuboid cells with scant cytoplasm, round to ovoid nuclei, and inconspicuous nucleoli, while in the groups rosettelike structures could be discerned. Only by integrating the data of clinical history, inspection, palpation, reaction on breast puncture, and immunologic findings could the diagnosis be made.