The kinetics of the visible growth of a primary melanoma reflects the tumor aggressiveness and is an independent prognostic marker: a prospective study

Primary melanoma (MM) could be a good model to test an intuitive concept: a cancer that is growing fast in its early phase is likely to have a high aggressiveness. Since MMs are visible tumors, many patients can provide information to indirectly assess the kinetics of their lesion. A prospective study was designed to assess if the kinetics of the visible growth of a primary MM, as described by the patient, could be a noninvasive prognostic marker. The ratio of MM thickness to delay between MM appearance and MM removal was used as a surrogate value for the kinetics of the MM growth. To assess the delay between MM appearance and removal, 362 patients with self-detected invasive MM fulfilled a detailed questionnaire, which provided 2 types of estimations of this delay and thus 2 melanoma kinetics indexes (MKI and MKI*). After a median follow-up of 4 years, univariate and multivariate analyses assessed whether relapse-free survival was linked to MKI or MKI*. MKI was significantly predictive of relapse-free survival (HR = 1.84 [1.51-2.25]) and relapse at 1 year (RR = 2.93 [1.84-4.69]), independently from Breslow thickness. MKI was retained in multivariate prognostic models, just after thickness and before other usual markers. MKI* was also a significant independent risk marker, although less predictive. In this model, the initial growth kinetics of a cancer reflects its aggressiveness and a high index predicts a short-term relapse. The "subjective" data obtained from patients about their MM history, although usually neglected, can thus provide a better prognostic marker than many "objective" tests.     

Homeostatic regulation of sleep in a genetic model of depression in the mouse: effects of muscarinic and 5-HT1A receptor activation.

In depressed patients, sleep undergoes marked alterations, especially sleep onset insomnia, sleep fragmentation, and disturbances of the Rapid Eye Movement (REM) sleep. Abnormalities of rest-activity rhythms and of hypothalamic-pituitary-adrenocortical function have also been described in these patients. In the present study, we examined the presence of such abnormalities in a recently developed line of mice (Helpless mice-H) that exhibit depression-like behaviors in validated tests, compared to the nonhelpless (NH) line derived from the same colony. Experiments were essentially carried out in females for which previous studies showed marked differences between H and NH lines. Compared to NH mice, the H line exhibited (i) lower basal locomotor activity, (ii) sleep fragmentation, shift towards lighter sleep stages, and facilitation of REM sleep reflected by increased amounts and decreased latency, (iii) larger response to the REM sleep promoting effect of muscarinic receptor stimulation (by arecoline). In contrast, H and NH mice were equally responsive to the REM sleep inhibitory effect of 5-HT1A receptor stimulation (by 8-OH-DPAT). In addition, a deficiency in delta power enhancement after sleep deprivation was observed in the H group, and acute immobilization stress in this group failed to elicit a REM sleep rebound and was associated with a long-lasting raise in serum corticosterone levels. These results further validate H mice as a depression model and suggest they might be of particular interest for investigating the neurobiological mechanisms and possibly genetic substrates underlying sleep alterations associated with depression.     

Pattern of hearing loss in a rat model of cochlear implantation trauma.

HYPOTHESIS: Trauma caused by cochlear implant electrode insertion is attributable to the combination of direct physical trauma and the delayed cell death of oxidative stress-injured auditory sensory cells. BACKGROUND: Histologic evaluation of cochlear implant electrode trauma has demonstrated that the extent of sensory cell losses is proportional to the degree of injury. However, the impact of delayed oxidative stress within injured cochlear tissues and the progressive loss of injured hair cells by way of apoptosis are at present unknown. METHODS: Laboratory rats were evaluated for hearing acuity before and after electrode insertion, before and after round window membrane incision only. Hearing was measured before trauma or incision and over the next 7 days. Objective measurements of hearing function were distortion products of otoacoustic emissions (DPOAEs) in the frequency range of 2 to 32 kHz and tone-burst (i.e., 4-32 kHz) evoked auditory brain stem responses (ABRs). RESULTS: For the experimental cochleae, there were progressive increases in ABR thresholds and decreases in ABR amplitudes. The amplitude of the DPOAEs in the experimental cochleae also showed progressive decreases. For the contralateral control and round window membrane surgical control ears, there were no significant changes in either DPOAE or ABR thresholds. CONCLUSION: These results document a progressive loss of hearing acuity postimplantation and strongly suggest that electrode insertion trauma generated oxidative stress within injured cochlear tissues.     

Hereditary angioneurotic edema: a case report in a 3-year-old child]

Hereditary angioneurotic edema is a dominant autosomal disease (incidence 1/150,000), whose diagnosis is crucial as this condition can lead to fatal asphyxia within minutes. We report the case of a three-year-old girl, misdiagnosed as allergic asthma. Recognition of the syndrome led to adapted care restoring normal family and school life. Pathogenic cascades involved and therapeutic principles of this disease are reviewed.     

Video-mediastinoscopy in management of patients with lung cancer: a preliminary study

Cervical mediastinoscopy is widely employed for biopsy of mediastinal lymph nodes and staging of lung cancer. The application of video-assisted technology to mediastinoscopy in a series of patients with lung cancer has not been reported. Preliminary experience with the use of video-mediastinoscopy in diagnosis and staging of lung cancer is presented. Fifteen patients with lung cancer were studied. Results of previous computed tomography scans had shown the presence of enlarged mediastinal lymph nodes in the retrovascular plane in all of the cases. Video-mediastinoscopy was performed under general anesthesia using a specifically designed rigid scope connected to a mono-charged-coupled device video camera (model INH 002756; Karl Storz-Endoskope, Tuttlingen, Germany). Neither fatalities nor major complications related to the procedure were observed. In all cases, video-mediastinoscopy proved useful for diagnosis or staging of lung cancer, therefore contributing to clinical decision making. The optimal visualization of mediastinal structure and the possibility for the surgeon to operate with both hands are appreciable characteristics of this technique.     

Vestibular functions in patients with tinnitus only

Objective: Tinnitus is the perception of sound in the ears or head without any external or internal acoustic stimulation, and it is usually associated with hearing loss. In addition, it has been reported that there is a relationship between vestibular problems and sensorineural hearing loss. The aim of this study was to evaluate the vestibular function in patients with tinnitus without hearing loss.

Methods: A total of 32 patients who complained only of tinnitus without hearing loss and 30 control subjects without tinnitus or hearing loss were included in this study. Oculomotor and caloric tests were performed on all subjects with videonystagmography. The tinnitus handicap inventory questionnaire, side and duration of tinnitus were recorded in all patients.

Results: The caloric test was abnormal in 13 of 32 (40.6%) patients in the tinnitus group and was normal in all of the control group. Abnormal caloric responses in patients with severe tinnitus were more frequent than in patients with mild or moderate tinnitus. There was a statistically significant difference in the optokinetic gain values between the tinnitus and control groups.

Conclusion: A relationship between tinnitus and abnormal caloric responses was determined. Tinnitus may be the first symptom of vestibular dysfunction.     

Cholangiographic features in fibrosis and cirrhosis of the liver

The cholangiographic features of intrahepatic bile ducts associated with cirrhosis or fibrosis are not well known. In order to achieve a radiological—pathological correlation, we studied nine livers with fibrosis or cirrhosis excised at autopsy. Cholangiograms were obtained within 24 hr after death from the nonfixed liver and multiple tissues samples were taken for histologic examination. Radiological data were interpreted by two independent investigators blinded to the clinical and histological findings. Cirrhosis (alcoholic in 4, posthepatitis in two) was observed in six livers, fibrosis (alcoholic in 2, posthepatitis in one) in three. No liver with fibrosis had cholangiographic abnormalities. In contrast, cholangiography of all livers with cirrhosis was abnormal. Abnormalities were a diminished arborization, a decrease of the distal opacification, an irregularity of caliber, and a tortuous course of the bile ducts. Histological study showed that the irregular and tortuous course were due to compression of the bile ducts by regenerative nodules. Furthermore, a thick fibrosis was organized around the bile ducts. In conclusion, fibrosis alone was not associated with cholangiographic abnormalities. In cirrhotic livers, intrahepatic bile ducts showed an irregular and tortuous course, a diminished arborization and a decrease of the distal opacification. These abnormalities were secondary to the presence of regenerative nodules and fibrosis organized around the bile ducts.     

Destruction of noradrenergic cell bodies by intracerebral 6-hydroxydopamine in the newborn rat

Intracerebral injections of 6-hydroxydopamine directly in the nucleus locus coeruleus were performed in 4-day-old rats. The effects of such treatment on the subsequent development of this nucleus were analyzed and compared to those obtained in vehicle-injected age-paired controls. The 3 histological techniques used (Nissl, Glenner reaction, and histochemical fluorescence) indicated in the experimental group a progressive disappearance of the coerulean perikarya within 7 days postinjection. This lesion was permanent and did not induce any noradrenergic sprouting.     

Tachon's syndrome (suracute back and/or thoracic pain following local injections of corticosteroids). A report of 318 French cases

OBJECTIVES: To assess the frequency, features, and outcome of excruciating lumbar, dorsal, and/or thoracic pain following injections of local corticosteroids in rare instances. METHODS: A questionnaire mailed to 500 French rheumatologists. RESULTS: Three hundred and eighteen cases were reported by 92 rheumatologists (one event per 8000 injections or 6.5 years of practice), following injections into lumbar epidural space (39%), an upper limb (30%), a lower limb (mostly the heel) (24%), or other locations (7%), of cortivazol (67%), hydrocortisone (25%), betamethasone (7%), or paramethasone (1%). Symptoms occurred 1-5 min (78%) or less than 1 min (22%) after injection, and highly acute axial pain usually lasted for less than 5 min (34%) or 5-15 min (51%). In addition to pain in lumbar (84%) and/or dorsal regions (25%) [often preceded or associated with thoracic pain (36%)], other signs were: anxiety (87%), shortness of breath (64%), facial flushing (64%), diffuse sweating (41%), agitation (29%), transient cough (23%), abdominal pain (20%), transient hypertension (15%), paleness (10%), hypotension (8%), diarrhoea (3%) and headache (3%). None of these patients was known to be allergic, and urticaria developed in only 2%. Outcome was favourable in all cases (even though 4/318 patients were transiently hospitalised) with an overall duration of 25 +/- 71 min. Another injection was performed later in 146/318 cases (46%), but Tachon's syndrome recurred in only 20 of these 146 patients (14%). CONCLUSION: The outcome of this impressive syndrome seems excellent. Tachon's syndrome might be the venous counterpart of Nicolau's syndrome (injection of corticosteroids in an artery).