High Percentage Of Lesions Research Articles

Lesions of the biliary system in Atlantic salmon (Salmo salar L.).

Lesions of the biliary system in Atlantic salmon (Salmo salar L.).

Взаимосвязь между состоянием кислотообразующей функции желудка и инвазией H. рylori при гастродуоденитах у детей

Актуальность. Хронические гастродуодениты возникают вследствие длительного воздействия на организм эндогенных и экзогенных причин. В регуляции кислото­образующей активности париетальных клеток участвуют как стимулирующие, так и подавляющие механизмы. Увеличение выделения гастрина антральным отделом желудка может развиваться также вследствие инфицирования Н. pylori. Цель исследования: оценить взаимосвязь между состоянием кислотообразующей функции желудка и инвазией H. pylori при хронических гастродуоденитах у детей. Материалы и методы. Обследованы 60 детей школьного возраста с диагнозом хронической неосложненной гастродуоденальной патологии. Всем детям проведено эндоскопическое исследование верхних отделов пищеварительного тракта, определены кислотообразующая и секреторная функции желудка. Диагностику инфекции H. pylori у детей проводили с помощью иммуноферментного анализа. Статистическую обработку полученных данных осуществляли с помощью программ Microsoft Office Exсel и Statistica 6.1. Результаты. Определив уровень кислотообразующей и секреторной функции обследованных детей, получили следующие результаты: пониженная секреторная и кислотообразующая функция наблюдалась у 9 детей, сохраненная — у 29, повышенная — у 12 детей, неопределенная — у 10 детей с эрозивными гастродуоденитами. При определении наличия H. рylori иммуноферментным методом у 28 (46,7 %) детей наблюдался низкий титр антител, у 14 (23,3 %) — средний, у 18 (30,0 %) — высокий. У пациентов с хроническими эрозивными и гипертрофическими гастродуо­денитами выявляли больший процент поражения слизистой оболочки желудка и двенадцатиперстной кишки H. рylori, чем у детей с хроническими поверхностными гастродуоденитами, как при эндоскопическом, так и при серологическом исследовании. Выводы. У обследованных детей выявлена четкая взаимосвязь между состоянием кислотообразующей и секреторной функции желудка и инвазией H. рylori, что зависит от степени органического поражения слизистой оболочки у них.

Treatment of recurrent aphthous stomatitis (RAS; aphthae; canker sores) with a barrier forming mouth rinse or topical gel formulation containing hyaluronic acid: a retrospective clinical study

BackgroundUse of hyaluronic acid-based products has become a valuable alternative to drug-based approaches in the treatment of recurrent aphthous stomatitis (RAS). The presented study aimed to investigate the effect of a barrier forming hyaluronic acid containing mouth wash or a topical gel formulation on the healing of RAS and patient’s quality of life.MethodsFor this single-center retrospective study, medical records of the Dental School of the University of Brescia were screened for adult and systemically health patients suffering from minor recurrent aphthous stomatitis (RAS) and treated with either a barrier forming, hyaluronic acid containing mouth wash (GUM® AftaClear® rinse) or a topical gel (GUM® AftaClear® gel) in 2015. All patients fulfilling the in−/exclusion criteria and presenting full data sets on lesion diameter, lesion color, as well as pain perception for baseline (day 0) and 4 and 7 days after treatment were enrolled into the presented study.ResultsOut of 60 screened patients, a total of 20 patients treated with the Rinse formulation and 25 treated with the Gel formulation were eligible for the enrollment into this study. Both groups showed equal distribution in patient’s age, sex and presented a similar mean lesion size (3.0 ± 1.0 mm), lesion color distribution as well as pain perception at baseline. All patients showed significant normalization of lesion color, reduction of pain, and lesion dimension within the course of their treatment. After 7 days, the mean percentage of lesion reduction was highly significant for both groups attaining 77.4 ± 30.1% in the Rinse group and 81.2 ± 23.1% in the Gel group with a complete lesion closure obtained in 60 and 56% of the cases, respectively. However, a significant (p < 0.05) higher percentage of lesions in the Gel group (72%) compared to the Rinse group (40%) showed an improvement in lesion size already after 3 days.ConclusionsWithin the limitation of retrospective design, it can be concluded that both the barrier forming hyaluronic acid containing mouth rinse as well as the topical gel formulation are effective in the treatment of minor recurrent aphthous stomatitis (RAS), with a trend for an earlier healing onset for the topical Gel formulation.

Atypical granuloma formation in Mycobacterium bovis-infected calves.

Bovine tuberculosis is a chronic inflammatory disease that causes granuloma formation. Characterization of granulomatous lesions of Mycobacterium bovis (M. bovis) experimentally infected cattle has helped to better understand the pathogenesis of this disease. However, few studies have described granulomas found in M. bovis naturally infected cattle. The aim of this work was to examine granulomas from Holstein-Friesian cattle naturally infected with M. bovis from a dairy basin located in the central region of Mexico. Tissue samples from thirty-two cattle with lesions suggestive of tuberculosis were collected post-mortem. Fifteen of the 32 sampled animals (46.8%) were 4 months of age or younger (calves), whereas the rest (53.2%, 17/32) were over one year old (adults). Macroscopic lesions suggestive of tuberculosis were found in the mediastinal lymph node chain of all animals (32/32). From the 1,143 granulomatous lesions that were microscopically analyzed, 34.6% (396/1143) were collected from adult animals and subsequently classified according to the nomenclature suggested by Wangoo et al., 2005. Surprisingly, lesions from calf tissues showed an atypical pattern which could not be fitted into the established developmental stages of this classification. Granulomatous lesions found in calves covered most of the affected organ, histologically showed large necrotic areas with central calcification, absence of a connective tissue capsule, and few giant cells. Also, there was a higher percentage of lesions with acid-fast bacilli (AFB) when compared to studied granulomas in adults. Growth of Mycobacterium spp was detected in 11 bacteriological tissue cultures. Genotypic identification of M. bovis was performed by DNA extraction from bacterial isolates, formalin-fixed and paraffin-embedded (FFPE) tissues and samples without bacterial isolation. M. bovis was detected by PCR in 84.3% (27/32) of the studied cases; whereas other AFB were observed in tissues of the remaining sampled animals (5/32). Our results describe atypical granuloma formation in calves 4 months of age or younger, naturally infected with M. bovis. These findings contribute to better understanding the physiopathology of M. bovis infection in cattle.

Advanced sinonasal malignancy – therapeutic challenge

Maxillofacial tumors are rare malignancies that constitute about 0.2-0.5% of all human malignancies. The initial symptoms of the disease are non-typical and imitate inflammation of paranasal sinuses. Most often, patients report one-sided nasal obstruction with bloody and purulent discharge and headaches. In addition to physical examination - often with the use of endoscopic nasal cavity assessment, it is necessary to perform computed tomography of the paranasal sinuses and magnetic resonance for accurate assessment of the extent of the lesions. Histopathological examination of tumor specimens is necessary for making the final diagnosis and planning treatment. Squamous cell carcinoma is the most common histological type in the sinonasal region. Other common malignancies in this area include adenocarcinoma, carcinoma adenoides cysticum, lymphomas, melanoma, and olfactory neuroblastoma. The treatment of choice of all malignant changes in the sinonasal complex, except for lymphomas, is surgical treatment. Unfortunately, a still high percentage of lesions is diagnosed at an advanced stage of the disease, when the infiltration includes the skull base. In these cases, the decision to perform a radical surgical treatment in the patient is very difficult and requires a lot of experience in the surgery of the skull base. However, due to the low radiosensitivity and low effectiveness of chemotherapy in sinonasal malignancy, resection of lesions and complementary treatment contribute to the prolongation of overall survival in this group of patients. The article discusses the cases of two patients with advanced cancer of the sinonasal complex reffered to the Otolaryngology Department of the Medical University of Warsaw.

Conventional MRI to detect the differences between mass-like tuberculosis and lung cancer.

The aim of this study was to investigate differences in the imaging features of mass-like tuberculosis and lung cancer on conventional MR sequences to improve the diagnostic ability for pulmonary masses. Thirty patients with suspicious pulmonary lesions were enrolled and diagnosed with tuberculosis by pathology or comprehensive clinical diagnoses. Twenty-six cases of lung cancer were retrospectively analyzed. Transverse fat-suppressed T2-weighted (T2W) imaging and T1-weighted (T1W) imaging were obtained at 1.5 Tesla. The imaging characteristics of lesions on the T2W and T1W images were compared between the two groups. The imaging features of enlarged mediastinal lymph nodes on T2W images were studied and compared. On T2W images, there was a higher percentage of lesions containing hypointensity in the tuberculosis group (GTB) than in the lung cancer group (GLC) (P=0.004).The incidence of lesions demonstrating heterogeneous intensity was significantly greater in the GTB than in the GLC (70.0% vs. 7.7%, P=0.001). Approximately 92.3% of the lung cancer cases showed hyperintensity, a proportion substantially greater than that in the GTB (6.7%). On T1W images, more cases showed hyperintensity in the GTB than in the GLC (43.3% vs. 7.7%, P=0.003). The signal intensity ratios (SIRs) of the lesion to rhomboid muscle on T2W and T1W images were significantly different between the two groups. The mean intrasubject standard deviation (SD) of lesions in the GTB was markedly greater than that in the GLC on both T2W and T1W images. Benign mediastinal lymph nodes in the GTB showed a variety of signals on T2W images, whereas 80% of metastatic mediastinal lymph nodes displayed slight homogeneous hyperintensity, and this difference between the two groups was statistically significant. Conventional MR sequences can reveal the essential differences between mass-like tuberculosis and lung cancer and may be helpful for discriminating pulmonary masses.

Identification of factors associated with treatment refractoriness of oral lesions in pemphigus vulgaris.

The oral mucosal lesions of patients with pemphigus vulgaris are known to show more treatment refractoriness than skin lesions. To identify which clinical and laboratory parameters may indicate treatment refractoriness of oral lesions in pemphigus vulgaris. This was a prospective study of 50 adults with pemphigus vulgaris and oral lesions; patients were given treatment appropriate for overall disease severity. Treatment refractoriness was defined arbitrarily as less than 75% reduction in oral objective Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) after treatment for 6 months. Of 46 patients who completed the study, 17 (37%) were treatment refractory whereas 29 (63%) were treatment responsive. At baseline, the treatment refractory group had a significantly longer mean duration of disease (P = 0·02) and mean duration of oral lesions (P = 0·01), a higher percentage of lesions in the retromolar trigone (P = 0·05) and on the occlusion line along the buccal mucosa (P = 0·04), a higher percentage of deep/crateriform ulcers (P < 0·001) and erosions with a lichenoid hue (P < 0·001). Herpes simplex virus (HSV) DNA positivity, assessed by polymerase chain reaction in oral tissue scrapings (P = 0·02), was also significantly higher in the treatment refractory group. No other factors we tested for were statistically significant. Treatment refractoriness of oral lesions was significantly associated with duration of disease/oral lesions; specific morphology and location of oral lesions; and the presence of HSV DNA in the oral cavity. These factors may forewarn the treating physician about a refractory course of oral lesions that may help with counselling patients.

Factors associated with speech-language disorders in motorcycle accident victims.

To investigate factors associated with speech-language disorders in victims of motorcycle accidents. This is a cross-sectional study. Victims of motorcycle accidents studied were treated at Hospital da Restauração between June and July 2014. The data were collected by consulting the records and direct interviews with these, at admission and after discharge. For analysis were raised single frequencies, average and chi-square test or Fisher's exact test. The margin of error used in the statistical tests was 5%, and the intervals were obtained with 95% reliability. 99 individuals were studied, 90.9% male, the mean age of 32.7 years. It found a high percentage of 42.3% of drunk drivers and 51.5% were not enabled. The Head Injuries were present in 30.3% of cases. The most affected body area were the lower limbs (71.7%), followed by the head and face region (56.6%). It was also found that 30.3% had complaints of speech pathology after hospital discharge and a statistically significant association between speech therapy complaint and not enabled (p=0.012) and collisions between bikes (p=0.004). There was a high percentage of lesions in the head and face resulting from accidents, associated mainly not eligible to drive bike and collisions between motorcycles, suggesting that these factors can aggravate injuries speech therapy.

Ultra-High-Field MRI Visualization of Cortical Multiple Sclerosis Lesions with T2 and T2*: A Postmortem MRI and Histopathology Study.

At 7T MR imaging, T2*-weighted gradient echo has been shown to provide high-resolution anatomic images of gray matter lesions. However, few studies have verified T2*WI lesions histopathologically or compared them with more standard techniques at ultra-high-field strength. This study aimed to determine the sensitivity of T2WI and T2*WI sequences for detecting cortical GM lesions in MS. At 7T, 2D multiecho spin-echo T2WI and 3D gradient-echo T2*WI were acquired from 27 formalin-fixed coronal hemispheric brain sections of 15 patients and 4 healthy controls. Proteolipid-stained tissue sections (8 μm) were matched to the corresponding MR images, and lesions were manually scored on both MR imaging sequences (blinded to histopathology) and tissue sections (blinded to MR imaging). The sensitivity of MR imaging sequences for GM lesion types and white matter lesions was calculated. An unblinded retrospective scoring was also performed. If all cortical GM lesions were taken into account, the T2WI sequence detected slightly more lesions than the T2*WI sequence: 28% and 16%, respectively (P = .054). This difference disappeared when only intracortical lesions were considered. When histopathologic information (type, location) was revealed to the reader, the sensitivity went up to 84% (T2WI) and 85% (T2*WI) (not significant). Furthermore, the false-positive rate was 8.6% for the T2WI and 10.5% for the T2*WI sequence. There is no strong advantage of the T2*WI sequence compared with a conventional T2WI sequence in the detection of cortical lesions at 7T. Retrospectively, a high percentage of lesions could be detected with both sequences. However, many lesions are still missed prospectively. This could possibly be minimized with better a priori observer training.

Endoscopic resection for superficial colorectal neoplasia in Italy: A prospective multicentre study

Since there are few prospective studies on colorectal endoscopic resection to date, we aimed to prospectively assess safety and efficacy of endoscopic resection in a cohort of Italian patients. Prospective multicentre assessment of resection of sessile polyps or non-polypoid lesions ≥10mm in size or smaller (if depressed). Outcome measures included complete excision, morbidity, mortality, and residual/recurrence at 12 months. Overall, 1012 resections in 928 patients were analysed (62.4% sessile polyps, 28.8% laterally spreading tumours, 8.7% depressed non-polypoid lesions). Lesions were prevalent in the proximal colon. En bloc resection was possible in 715/1012 cases (70.7%), whereas piecemeal resection was required in 297 (29.3%). Endoscopically complete excision was achieved in 866 cases (85.6%). Adverse events occurred in 83 (8.2%), and no deaths occurred. Independent predictors of 12-month residual/recurrence were the location of the lesion in the proximal colon (OR 2.22 [95% CI 1.16-4.26]; p=0.015) and piecemeal endoscopic resection (OR 2.76 [95% CI 1.56-4.87]; p=0.0005). Limitations of the study were: potential expertise bias, no data on eligible and potentially resectable excluded lesions, high percentage of lesions<20mm, follow-up limited to 1 year. In this registry study the endoscopic resection of colorectal lesions was safe and achieved high rates of long-term endoscopic clearance.

Angiographic maximal luminal diameter and appropriate deployment of the everolimus-eluting bioresorbable vascular scaffold as assessed by optical coherence tomography: an ABSORB cohort B trial sub-study

Bioresorbable vascular scaffolds (BVS) present different mechanical properties as compared to metallic platform stents. Therefore, the standard procedural technique to achieve appropriate deployment may differ. Fifty-two lesions treated with a 3 x 18 mm BVS were imaged with optical coherence tomography (OCT) post-implantation and screened for parameters suggesting non-optimal deployment. These included minimal scaffold area (minSA)<5 mm², residual area stenosis (RAS)>20%, edge dissections, incomplete scaffold/strut apposition (ISA)>5% and scaffold pattern irregularities. The angiographic proximal and distal maximal lumen diameters (DMAX) were measured by quantitative coronary angiography. Based on the DMAX values, the population was divided into three groups: DMAX <2.5 mm (n=13), DMAX between 2.5-3.3 mm (n=30) and DMAX >3.3 mm (n=9). All three groups presented with similar pre-implantation angiographic characteristics except for the vessel size and were treated with similar balloon/artery ratios. The group with a DMAX <2.5 mm presented with a higher percentage of lesions with minSA <5 mm² (30.8% vs. 10.0% vs. 0%; p=0.08) and edge dissections (61.5% vs. 33.3% vs. 11.1%; p=0.05). Lesions with >5% of ISA were significantly higher in the group with DMAX >3.3 mm (7.7% vs. 36.7% vs. 66.7%; p=0.02). RAS >20% was similar between all groups (46.2 vs. 53.3 vs. 77.8%; p=0.47) and scaffold pattern irregularities were only documented in three cases. BVS implantation guided with quantitative angiography may improve the OCT findings of optimal deployment. The clinical significance of these angiographic and OCT findings warranted long term follow-up of larger cohort of patients.

Ten-Year Longitudinal Changes in Retinal Microvascular Lesions: The Atherosclerosis Risk in Communities Study

There are limited data on the natural history and longitudinal changes of retinal microvascular lesions. We examined 10-year changes in retinal microvascular lesions, focusing on those related to hypertension and shown to predict development of cardiovascular disease. Prospective cohort. We included 1120 middle-aged participants without diabetes of the Atherosclerosis Risk in Communities (ARIC) Study in 1993 to 1995 and again 10 years later in 2003 to 2005. Retinal microvascular lesions were graded from retinal photographs using the same protocol at both examinations, with changes (incidence or disappearance) adjudicated by a side-by-side comparison of photographs. The study sample was stratified by carotid intima media thickness (IMT) and ARIC field center; thus, all analyses were weighted by these factors. Persons with diabetes were excluded because the frequency and pathophysiology of diabetic retinal lesions is different. Incidence and disappearance rates of lesions. The 10-year incidence of focal arteriolar narrowing, arteriovenous (AV) nicking, and retinopathy in persons without diabetes was 3.4% (95% confidence interval [CI], 2.3-4.9), 2.5% (95% CI, 1.6-3.9), and 2.2% (95% CI, 1.3-3.5) respectively. Over the 10-year period, of 32, 219, and 24 eyes with focal arteriolar narrowing, AV nicking and retinopathy at baseline, 50.3% (95% CI, 28.6-71.9), 40.7% (95% CI, 32.7-49.4), and 65.9% (95% CI, 42.4-83.5), respectively, disappeared. Higher baseline plasma fibrinogen and white cell counts were associated with incident focal arteriolar narrowing; antihypertensive medication use was associated with incident AV nicking, and higher diastolic blood pressure, carotid IMT, and white cell counts were associated with incident retinopathy. Higher fasting serum glucose was not significantly associated with incident retinopathy, although this may be related to the small number of lesions (odds ratio, 5.88; 95% CI, 0.74-46.64 per standard deviation difference). In this sample of middle-aged adults, new retinal microvascular lesions appeared at a rate between 2% and 4% over 10 years. A high percentage of lesions (≥40%) disappeared over the same period, suggesting considerable remodeling in the retinal microvasculature. The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Safety and efficacy of biopsy of renal masses guided by ultrasound

Aim: Biopsy of renal masses has been controversially discussed since (1) a high percentage of lesions are thought to be malignant (2) the method is dangerous and (3) reveals a high rate of unconclusive findings. Recently a larger number of small renal tumors are reported at time of diagnosis with a relative high rate of benign lesions. Here we report on ultrasound-guided (us) renal biopsy of renal lesions to avoid operation.

CCL5 and CCR5 genotypes modify clinical, radiological and pathological features of multiple sclerosis

Chemokines mediate selective recruitment of leukocyte subsets into the CNS during inflammatory episodes. We hypothesised that functional polymorphisms in CCR5 and CCL5 influence perivascular leukocyte infiltration, inflammation, axonal loss, and remyelination, and disease course. Therefore, we determined genotypes at four possibly functional polymorphisms in CCR5 and CCL5 for 637 patients and 92 brain donors with multiple sclerosis (MS). For a subset of 192 patients, MRI data were available. We found that low-producer allele CCL5–403 ⁎G was associated with reduced risk of severe axonal loss, whereas high-producer allele CCL5–403 ⁎A was associated with a worse clinical disease course measured by the MS Functional Composite Score and MS Severity Score. Low-producer allele CCR5 + 303 ⁎G was associated with reduced T2 hyperintense and T1 hypointense lesion volumes on MRI, and high-producer allele CCR5 + 303 ⁎A with early age at onset. Furthermore, low-producer allele CCR5Δ32 was associated with reduced T2 lesion volume, lower black hole ratio on MRI, and with a higher percentage of lesions with signs of remyelination, histopathologically. In summary, our multifaceted study supports the notion that polymorphisms in CCL5 and CCR5 modify the course of MS.

Detection of epidermodysplasia verruciformis-like human papillomavirus types in malignant and premalignant skin lesions of renal transplant recipients.

To evaluate the putative role of human papillomaviruses (HPV) in the development of skin cancer in renal transplant recipients, a series of skin biopsies from premalignant and malignant skin lesions was analysed using the polymerase chain reaction. Four different consensus primer pairs were used. HPV DNA was detected in five of 24 cases of squamous cell carcinoma, in one of three cases of Bowen's disease, in none of four basal cell carcinomas, in two of seven cases of actinic keratosis and in one of five cases of keratoacanthoma. Typing by direct sequencing of the amplified HPV DNA was possible in seven of nine cases, and revealed epidermodysplasia verruciformis (EV)-associated HPV types, or HPV types related to EV-associated types. Hence, HPV DNA could be detected in a significant proportion of (pre)malignant skin tumours in renal transplant recipients. The finding that some of the detected HPV types were as yet uncharacterized EV-related types, suggests that HPV DNA could be present in a higher percentage of lesions, and might be detected with refinement of the techniques.

Microcalcificaciones con diagnóstico de benignidad en biopsia con aguja gruesa (14G): seguimiento y falsos negativos en 76 casos

AimRetrospective study of the usefulness of 14G needle biopsy in predicting benignity of breast microcalcifications. Materials and MethodsSeventy-six biopsies were performed between 1998 and 2001 on microcalcifications with benign diagnosis using conventional stereotactic, automated, large core (14 gauge) needle (more than 5 cylinders), with microcalcifications having been diagnosed radiologically (67%) and histologically (83%). There were included no high risk lesions.All findings were classified as either concordant or non-concordant. Non-concordant findings underwent subsequent exscisional biopsy. Follow-up was prescribed in cases of unspecific results. Excisional biopsy was indicated during follow-up should any mammographic changes have been observed.There were realized follow-up periods of at least 2 years. All cases were submitted to histological correlation. ResultsForty-two biopsies (55%) presented unspecific results. Excisional biopsy due to non-concordant results was performed in 9 cases (12%), with 2 false negatives (2.6%). Sixty-two cases (81%) were controlled, there being incomplete follow-up in 14 cases (58%).There were observed mammographic changes in lesions in 6 biopsies (8%). The time interval between initial diagnosis and mammo-graphic change varied from 6 to 35 months, with the average being 22 months. No false negatives were observed after excisional biopsy. ConclusionsThick needle biopsy (14 gauge) proved to be definitive in 55% of histologically unspecific results, which necessitated brief follow-ups. It also did so for 12% of those biopsies performed due to non-concordance and 2.6% of false negatives.Any changes occurring late in the follow-up period suggested the possibility of extending such beyond two years in order to establish benignity. The absence of late occurring false negatives, as previously published, related both to the size of biopsy samples and to the fact that a relatively high percentage of lesions were BI-RADS 3 classified.

The time from diagnostic excision biopsy to wide local excision for primary cutaneous malignant melanoma may not affect patient survival.

The surgical management of primary cutaneous malignant melanoma usually involves an excision biopsy of the suspected lesion followed by wide local excision. No study has addressed whether a delay between these two surgical procedures influences patient outcome. To determine if the surgical interval (SI) between the diagnostic excision biopsy and wide local excision for primary cutaneous malignant melanoma affects recurrence or survival outcome. A cohort of 986 patients who had a diagnostic excision biopsy followed by wide local excision was identified from those registered on a specialist database that records the clinicopathological features, surgical treatment and follow-up information of all patients with malignant melanoma in Scotland. The cohort was divided into five arbitrary groups determined by the length of the SI as follows:< or =14 days, 15-28 days, 29-42 days, 43-91 days and > or = 92 days. Overall survival, disease-free survival and recurrence-free interval between the groups were compared univariately and multivariately. The mean age at excision biopsy was 47.4 years and the median period of follow-up was 5 years (range 27 days to 20.7 years). The median SI was 30 days (range 1-468 days). The SI was: (i)< or =14 days for 130 (13%); (ii) 15-28 days for 320 (33%); (iii) 29-42 days for 262 (27%); (iv) 43-91 days for 251 (25%); and (v) > or = 92 days for 23 (2%) patients. The latter group was older, had thinner melanomas, a higher percentage of lesions on the head and neck, fewer superficial spreading malignant melanomas and ulceration present less often compared with patients treated earlier. Univariately, there was no significant difference in overall survival (P = 0.60) or disease-free survival (P = 0.24) between the groups. Although there was a statistically significant difference in the percentage of recurrence-free patients between the groups (P = 0.011), the better recurrence-free rates occurred in the 29-42 and 43-91 day groups. After adjusting for age, sex, tumour thickness, site, histology, ulceration and mitotic activity using Cox's proportional hazards model, there was no statistically significant difference in overall survival, disease-free survival and recurrence-free percentages between the surgical groups (P = 0.88, P = 0.44 and P = 0.084, respectively). There was no evidence that survival outcome or recurrence was related to the time interval between the diagnostic excision biopsy and wide local excision of melanoma.

Expression profile of genes coding for melanoma differentiation antigens and cancer/testis antigens in metastatic lesions of human cutaneous melanoma.

Vaccination-based therapy of melanoma has so far mainly focused on monovalent approaches using either melanoma differentiation antigens or cancer/testis antigens. To study the complementarity of expression from these two families of antigens recognized by T-cells, we screened 47 metastatic lesions of cutaneous melanoma for the expression of three melanoma differentiation antigens and eight cancer/testis antigens using reverse transcription-polymerase chain reaction (RT-PCR). The melanoma differentiation antigens were expressed in a somewhat higher percentage of lesions (94% positive for at least one marker) than the cancer/testis antigens (91% positive for at least one marker). Nearly all the melanoma metastases (98%) expressed at least one of the markers tested. One melanoma metastasis was negative for all the markers. Two out of 47 lesions did not express any of the three differentiation markers but expressed one or more of the cancer/testis antigens, indicating some additional potential for these antigens compared with the melanoma differentiation antigens. Therefore, we conclude that polyvalent immunotherapy using multiple epitopes from both families of antigens might increase the eligibility of melanoma patients and the efficacy of the treatment.

Induction of cardiac anomalies with all-trans retinoic acid in the chick embryo

SummaryTo study the interaction between hemodynamics and morphology in abnormal development of the heart, it is essential to have an animal model with specific and reproducible cardiac malformations. A standardized method was developed for inducing such an anomaly in the chick embryo. For this purpose, all-trans retinoic acid, dissolved in 2% dimethylsulphoxide, was applied on the vitelline membrane of the embryo in concentrations of 1.0 μgm and 0.3 μgm. A total of 207 embryos, staged according to Hamburger and Hamilton, were treated at stages 10 (33 hours of incubation) and 15 (50–55 hours of incubation). Three control groups consisted of embryos solely treated with dimethylsulphoxide, sham operated chicks, and untreated embryos, respectively. The embryos were sacrificed on the 9th, 10th and 11th days of incubation and hearts were examined by microdissection. Additional histologic studies were undertaken in 110 cases. Embryos treated with retinoic acid at both stages of development showed a high percentage of lesions falling within the general spectrum of double outlet right ventricle. The abnormality varied from merely a rightward shift of the aorta to cases with an additional subaortic ventricular septal defect, which, in combination with the rightward positioned aorta, was classified as a double outlet right ventricle. Histologic examination showed the presence of muscular tissue between the leaflets of the aortic and mitral valves. No other types of cardiac malformations were seen. Our results, with respect to timing, resemble data from studies made of hearts after surgical ablation of neural crest at comparable stages. Both method and timing of treatment with retinoic acid are important factors for the induction of specific and reproducible cardiac anomalies. This chick model allows for further detailed study of development of double outlet right ventricle, as well as the assessment of early detectable hemodynamic changes.

The most common fragile site in man is 3p14.

In man a common fragile site is known to occur at 3p14. We studied the expression of this fragility in a group of 70 normal healthy subjects. Chromosome breaks, chromatid breaks and gaps at 3p14 could be observed in every examined individual, and in a total of 7000 metaphases they were seen in a mean of 4% of cells. Fluorescence studies in ten persons with chromosome No. 3 polymorphism showed that in all cases both Nos. 3 were about equally liable to breakage. A considerable variation in the fra 3p14 expression was found between individuals as well as in repeated cultures from the same person. Neither sex nor age influences could be detected. Cultures with a high percentage of lesions at 3p14 tended to have also a high number of lesions at other sites. Methotrexate and fluorodeoxyuridine markedly enhanced the expression of fra 3p14 and other fragilities. It is concluded that the chromosomal region at 3p14 represents man's most common fragile site, the expression of which seems to be influenced by environmental and heritable factors.