Prevalence of dermatitis including allergic contact dermatitis from medical devices used by children and adults with Type 1 diabetes mellitus: A systematic review and questionnaire study.

Use of medical devices (MDs), that is, glucose sensors and insulin pumps, in patients with Type 1 diabetes mellitus (T1D) has proven an enormous advantage for disease control. Adverse skin reactions from these MDs may however hamper compliance. The objective of this study was to systematically review and analyse studies assessing the prevalence and incidence of dermatitis, including allergic contact dermatitis (ACD) related to MDs used in patients with T1D and to compare referral routes and the clinical investigation routines between clinics being part of the European Environmental and Contact Dermatitis Research Group (EECDRG). A systematic search of PubMed, EMBASE, CINAHL and Cochrane databases of full-text studies reporting incidence and prevalence of dermatitis in persons with T1D using MDs was conducted until December 2021. The Newcastle-Ottawa Scale was used to assess study quality. The inventory performed at EECRDG clinics focused on referral routes, patient numbers and the diagnostic process. Among the 3145 screened abstracts, 39 studies fulfilled the inclusion criteria. Sixteen studies included data on children only, 14 studies were on adults and nine studies reported data on both children and adults. Participants were exposed to a broad range of devices. Skin reactions were rarely specified. It was found that both the diagnostic process and referral routes differ in different centres. Further data on the prevalence of skin reactions related to MDs in individuals with T1D is needed and particularly studies where the skin reactions are correctly diagnosed. A correct diagnosis is delayed or hampered by the fact that, at present, the actual substances within the MDs are not declared, are changed without notice and the commercially available test materials are not adequately updated. Within Europe, routines for referral should be made more standardized to improve the diagnostic procedure when investigating patients with possible ACD from MDs.

Is benzyl alcohol a significant contact sensitizer?

BACKGROUND: Benzyl alcohol is a widely used preservative, solvent and fragrance material. According to published data, it is a rare sensitizer in humans. OBJECTIVES: To identify characteristics and sensitization patterns of patients with positive patch test reactions to benzyl alcohol and to check the reliability of the patch test preparation benzyl alcohol 1% pet. PATIENTS AND METHODS: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2010-2019. RESULTS: Of 70 867 patients patch tested with benzyl alcohol 1% pet., 146 (0.21%) showed a positive reaction, most of them (89%) only weakly positive. The number of doubtful and irritant reactions significantly exceeded the number of positive reactions. Reproducibility of positive test reactions was low. Among benzyl alcohol-positive patients, compared to benzyl alcohol-negative patients, there were significantly more patients with leg dermatitis (17.8% vs. 8.6%), more patients aged 40 years or more (81.5% vs. 70.5%) and more patients who were tested because of a suspected intolerance reaction to topical medications (34.9% vs. 16.6%). Concomitant positive reactions were mainly seen to fragrances, preservatives and ointment bases. CONCLUSIONS: Sensitization to benzyl alcohol occurs very rarely, mainly in patients with stasis dermatitis. In view of our results, benzyl alcohol cannot be regarded as a significant contact allergen, and therefore marking it as skin sensitizer 1B and labelling it with H 317 is not helpful.

Man against machine reloaded: performance of a market-approved convolutional neural network in classifying a broad spectrum of skin lesions in comparison with 96 dermatologists working under less artificial conditions.

BACKGROUND: Convolutional neural networks (CNNs) efficiently differentiate skin lesions by image analysis. Studies comparing a market-approved CNN in a broad range of diagnoses to dermatologists working under less artificial conditions are lacking. MATERIALS AND METHODS: One hundred cases of pigmented/non-pigmented skin cancers and benign lesions were used for a two-level reader study in 96 dermatologists (level I: dermoscopy only; level II: clinical close-up images, dermoscopy, and textual information). Additionally, dermoscopic images were classified by a CNN approved for the European market as a medical device (Moleanalyzer Pro, FotoFinder Systems, Bad Birnbach, Germany). Primary endpoints were the sensitivity and specificity of the CNN's dichotomous classification in comparison with the dermatologists' management decisions. Secondary endpoints included the dermatologists' diagnostic decisions, their performance according to their level of experience, and the CNN's area under the curve (AUC) of receiver operating characteristics (ROC). RESULTS: The CNN revealed a sensitivity, specificity, and ROC AUC with corresponding 95% confidence intervals (CI) of 95.0% (95% CI 83.5% to 98.6%), 76.7% (95% CI 64.6% to 85.6%), and 0.918 (95% CI 0.866-0.970), respectively. In level I, the dermatologists' management decisions showed a mean sensitivity and specificity of 89.0% (95% CI 87.4% to 90.6%) and 80.7% (95% CI 78.8% to 82.6%). With level II information, the sensitivity significantly improved to 94.1% (95% CI 93.1% to 95.1%; P < 0.001), while the specificity remained unchanged at 80.4% (95% CI 78.4% to 82.4%; P = 0.97). When fixing the CNN's specificity at the mean specificity of the dermatologists' management decision in level II (80.4%), the CNN's sensitivity was almost equal to that of human raters, at 95% (95% CI 83.5% to 98.6%) versus 94.1% (95% CI 93.1% to 95.1%); P = 0.1. In contrast, dermatologists were outperformed by the CNN in their level I management decisions and level I and II diagnostic decisions. More experienced dermatologists frequently surpassed the CNN's performance. CONCLUSIONS: Under less artificial conditions and in a broader spectrum of diagnoses, the CNN and most dermatologists performed on the same level. Dermatologists are trained to integrate information from a range of sources rendering comparative studies that are solely based on one single case image inadequate.

Challenging a paradigm: skin sensitivity to sodium lauryl sulfate is independent of atopic diathesis.

BACKGROUND: Sodium lauryl sulfate (SLS) is the best-studied detergent in irritant contact dermatitis. In atopic dermatitis, the two major pathophysiological abnormalities concern skin barrier function and regulation of cutaneous immune responses. The probability of atopic skin diathesis can be assessed by comprehensive analysis of patient history, as well as clinical and laboratory findings, resulting in the Erlangen Atopy Score (EAS). OBJECTIVES: To investigate the impacts of (i) atopic skin diathesis according to the EAS and (ii) the physician-assessed diagnoses 'atopic dermatitis', 'allergic rhinitis' and 'allergic asthma' on SLS skin reactions. METHODS: This is a retrospective analysis of data from 2030 consecutive patients patch tested with SLS (0·25% aqueous) from two tertiary referral centres in Germany, from 2008 to 2014. RESULTS: Patients with a high probability of atopic skin diathesis showed no significant increase in positive SLS reactions compared with patients without atopic skin diathesis (14·2% vs. 16·8%). The grading of positive SLS skin reactions (1-4) revealed no differences in patients with or without atopic skin diathesis. Furthermore, diagnoses of atopic dermatitis, allergic rhinitis or allergic asthma had no impact on positive SLS skin reactions in multivariate logistic regression analysis. CONCLUSIONS: We found no association of increased skin irritability to SLS with atopic skin diathesis, atopic dermatitis, allergic rhinitis or allergic asthma in a large patient cohort. It therefore seems that the test of skin irritability with SLS, which is currently common practice in many centres, does not allow prediction of susceptibility to irritant eczematous inflammation in atopic vs. nonatopic individuals. What's already known about this topic? Irritant contact dermatitis and atopic skin diathesis share impaired skin barrier function as a pathophysiological pattern. Sodium lauryl sulfate (SLS) is tested at 0·25% aqueous as an irritant control in patch testing, and hence the results might be affected by atopic skin diathesis. What does this study add? Challenging a long-standing paradigm, we found no association of increased reactivity to SLS patch tests in individuals with atopic skin diathesis, atopic dermatitis, allergic rhinitis or allergic asthma in a large patient cohort. Thus, irritant control testing with SLS, which is useful in interpreting doubtful allergen patch test results, does not depend on individual atopy status.

Assessment of occupational exposure and spectrum of contact sensitization in metalworkers with occupational dermatitis: results of a cohort study within the OCCUDERM project.

BACKGROUND: Metalworkers occupationally exposed to metals, tools, metalworking fluids (MWFs), technical oils, gloves, skin care products etc. frequently suffer from occupational dermatitis (OD). OBJECTIVES: To investigate occupational exposure and to identify relevant occupational sensitizers in metalworkers with OD, and to evaluate suitability of current German patch test recommendations for this occupational group. PATIENTS AND METHODS: As part of the OCCUDERM project, occupational exposure of 230 metalworkers with suspected OD patch tested in the departments of dermatology in Göttingen and Osnabrück (both Lower Saxony, Germany) in 2012-2017 was recorded by questionnaire. These data, as well as results, of patch testing with standardized allergens and with workplace material were analysed. RESULTS: Metalworking fluids and skin care products were the most important exposures. Among MWF allergens, most frequently sensitizations to formaldehyde and formaldehyde releasers, colophony/abietic acid and monoethanolamine were observed. Sensitization to methylisothiazolinone (MI) was frequent, probably as part of the general European epidemic of contact allergy to MI in leave-on cosmetics. Sensitization to glove ingredients only played a minor role. CONCLUSIONS: The known occupational allergen spectrum could largely be confirmed. In order not to miss relevant sensitizations, patch testing with material from the patients' workplaces in parallel to baseline and MWF series is recommended. Sensitizations diagnosed could not always be linked to particular occupational exposures.

Diagnostic performance of a deep learning convolutional neural network in the differentiation of combined naevi and melanomas.

BACKGROUND: Deep learning convolutional neural networks (CNN) may assist physicians in the diagnosis of melanoma. The capacity of a CNN to differentiate melanomas from combined naevi, the latter representing well-known melanoma simulators, has not been investigated. OBJECTIVE: To assess the diagnostic performance of a CNN when used to differentiate melanomas from combined naevi in comparison with dermatologists. METHODS: In this study, a CNN with regulatory approval for the European market (Moleanalyzer-Pro, FotoFinder Systems GmbH, Bad Birnbach, Germany) was used. We attained a dichotomous classification (benign, malignant) in dermoscopic images of 36 combined naevi and 36 melanomas with a mean Breslow thickness of 1.3 mm. Primary outcome measures were the CNN's sensitivity, specificity and the diagnostic odds ratio (DOR) in comparison with 11 dermatologists with different levels of experience. RESULTS: The CNN revealed a sensitivity, specificity and DOR of 97.1% (95% CI [82.7-99.6]), 78.8% (95% CI [62.8-89.1.3]) and 34 (95% CI [4.8-239]), respectively. Dermatologists showed a lower mean sensitivity, specificity and DOR of 90.6% (95% CI [84.1-94.7]; P = 0.092), 71.0% (95% CI [62.6-78.1]; P = 0.256) and 24 (95% CI [11.6-48.4]; P = 0.1114). Under the assumption that dermatologists use the CNN to verify their (initial) melanoma diagnosis, dermatologists achieve an increased specificity of 90.3% (95% CI [79.8-95.6]) at an almost unchanged sensitivity. The largest benefit was observed in 'beginners', who performed worst without CNN verification (DOR = 12) but best with CNN verification (DOR = 98). CONCLUSION: The tested CNN more accurately classified combined naevi and melanomas in comparison with trained dermatologists. Their diagnostic performance could be improved if the CNN was used to confirm/overrule an initial melanoma diagnosis. Application of a CNN may therefore be of benefit to clinicians.

The frequency of specific contact allergies is reduced in patients with psoriasis.

BACKGROUND: Earlier studies suggested an inverse association between contact allergy and psoriasis, although the results of clinical studies have been inconsistent. Gene expression studies in human contact allergy focusing on immune responses revealed nickel being an inducer of T helper (Th)1/Th17 and some Th22 immune polarization, whereas fragrances were found to promote a Th2-dominated immune activation. OBJECTIVES: To investigate the epidemiological association between contact allergy and psoriasis in a large multicentre cohort and to analyse the sensitization profile to specific allergens in these patients. METHODS: Retrospective analysis of patch-tested patients from 56 departments of dermatology (1996-2015), including 2387 patients with psoriasis and 161 989 control patients. All patients with atopic dermatitis were excluded from both groups. RESULTS: The odds ratio (OR) for contact allergy was calculated to be 0·55 in patients with psoriasis (95% confidence interval 0·50-0·59). Logistic regression analyses with several independent variables indicated a 'protective effect' of having psoriasis for most allergens, independently of age, sex, affected body site and patch test indication. Fragrance mix II (OR 0·36) and lanolin alcohols (OR 0·38) were found to be among the least common allergens in patients with psoriasis. In contrast, the frequency of contact dermatitis to nickel was only marginally affected in patients with psoriasis compared with controls (OR 0·75). CONCLUSIONS: The inverse association between psoriasis and allergic contact sensitization is likely to be not exclusively mediated by psoriasis itself. The polarization of the activated immune response by specific allergens may influence the occurrence and significance of contact allergies in underlying immune-mediated diseases, eventually even beyond the skin.

Man against machine: diagnostic performance of a deep learning convolutional neural network for dermoscopic melanoma recognition in comparison to 58 dermatologists.

Background: Deep learning convolutional neural networks (CNN) may facilitate melanoma detection, but data comparing a CNN's diagnostic performance to larger groups of dermatologists are lacking. Methods: Google's Inception v4 CNN architecture was trained and validated using dermoscopic images and corresponding diagnoses. In a comparative cross-sectional reader study a 100-image test-set was used (level-I: dermoscopy only; level-II: dermoscopy plus clinical information and images). Main outcome measures were sensitivity, specificity and area under the curve (AUC) of receiver operating characteristics (ROC) for diagnostic classification (dichotomous) of lesions by the CNN versus an international group of 58 dermatologists during level-I or -II of the reader study. Secondary end points included the dermatologists' diagnostic performance in their management decisions and differences in the diagnostic performance of dermatologists during level-I and -II of the reader study. Additionally, the CNN's performance was compared with the top-five algorithms of the 2016 International Symposium on Biomedical Imaging (ISBI) challenge. Results: In level-I dermatologists achieved a mean (±standard deviation) sensitivity and specificity for lesion classification of 86.6% (±9.3%) and 71.3% (±11.2%), respectively. More clinical information (level-II) improved the sensitivity to 88.9% (±9.6%, P = 0.19) and specificity to 75.7% (±11.7%, P < 0.05). The CNN ROC curve revealed a higher specificity of 82.5% when compared with dermatologists in level-I (71.3%, P < 0.01) and level-II (75.7%, P < 0.01) at their sensitivities of 86.6% and 88.9%, respectively. The CNN ROC AUC was greater than the mean ROC area of dermatologists (0.86 versus 0.79, P < 0.01). The CNN scored results close to the top three algorithms of the ISBI 2016 challenge. Conclusions: For the first time we compared a CNN's diagnostic performance with a large international group of 58 dermatologists, including 30 experts. Most dermatologists were outperformed by the CNN. Irrespective of any physicians' experience, they may benefit from assistance by a CNN's image classification. Clinical trial number: This study was registered at the German Clinical Trial Register (DRKS-Study-ID: DRKS00013570; https://www.drks.de/drks_web/).

Melanoma thickness: the role of patients' characteristics, risk indicators and patterns of diagnosis.

BACKGROUND: Factors associated with early vs. late diagnosis of cutaneous melanoma remain poorly understood. OBJECTIVE: To identify factors with a significant impact on melanoma thickness. METHODS: Patients with previous melanoma (n = 347, median age at diagnosis: 56.5 years, 44.7% female, 55.3% male) were recruited for this monocentre, non-randomized, observational study between April 2012 and March 2013. All patients were assessed by means of a structured interview and systematic clinical and dermoscopic full-body examination. Melanoma thickness in association with patients' characteristics, risk indicators and patterns of diagnosis was submitted to statistical analyses. RESULTS: Univariate analyses revealed associations between a statistically significant lower Breslow thickness and participation in specialized dermoscopic screening programs, personal history of more than one previous melanoma, diagnostic examination with a dermatoscope, diagnostic examination by board certified dermatologist, high number of common and/or atypical nevi, younger age at time of diagnosis, higher level of education, or superficial spreading or lentigo maligna melanoma subtype (all P ≤ 0.01). In a multivariate regression analysis only three of these criteria: (i) participation in specialized screening programs (P < 0.0001); (ii) melanoma subtype (P < 0.0001); and (iii) diagnostic examination with a dermatoscope (P = 0.040) and one interaction term ('younger age' x 'female sex', P < 0.0001) showed an independent influence on a significantly lower melanoma thickness. CONCLUSIONS: The screening of patients in specialized surveillance programs resulted in melanoma detection at significantly earlier stages. The use of dermoscopy, SSM or LMM histotype and younger age in connection with female sex were also characteristics that were independently associated with significantly thinner melanomas in multivariate analyses.

[Symmetrically enlarging pigmented lesion in an adolescent]. / Symmetrisch wachsende Pigmentläsion bei einem Jugendlichen.

A 16-year-old boy with multiple nevi presented with an enlarging pigmented lesion on his right chest. Previously excised nevi were all benign. Dermoscopy of the symmetrical lesion revealed a trizonal globular-homogeneous pattern. A peripheral rim of brown globules was followed by a zone with homogeneous pigmentation. The centre of the lesion showed black dots and globules. Histopathology confirmed a dysplastic compound nevus and found no diagnostic aspects of pigmented spindle cell nevus (Reed).

Large speckled lentiginous naevus superimposed with Spitz naevi: sequential digital dermoscopy may lead to unnecessary excisions triggered by dynamic changes.

We report a 14-year-old girl with a large speckled lentiginous naevus (SLN) on her left arm and shoulder. As the occurrence of melanoma within SLN has been described previously, long-term follow-up of atypical lesions by digital dermoscopy was started at the age of 4 years. To date, nine Spitz naevi and four dysplastic compound naevi have been excised due to dynamic changes over time. No melanoma has so far been detected. We critically discuss the possibility of an 'overtreatment' because of a high rate of physiological changes within SLN of children. In conclusion, we would like to encourage a close follow-up of large SLN whenever complete excision is not an option. In order to avoid unnecessary excisions triggered by subtle dynamic changes, a standard approach with overview images, conventional dermoscopy and early excision of lesions that are rated as suspicious for melanoma by established algorithms may be recommended.

Carboxypeptidase-B-like processing of the C-terminus of glucagon-like peptide-2 in pig and human small intestine.

We developed specific, C-terminal radioimmunoassays for three proglucagon (PG) fragments: PG 151-158, PG 151-160 and PG 126-159 (glucagon-like peptide-2 (GLP-2] in order to determine the exact C-terminal sequence of the newly isolated GLP-2 in man and pig. The antigens and the antisera showed no mutual cross-reactivity. By gel filtration of extracts of pig and human small intestine, the immunoreactivity eluting at the position of GLP-2 was identified by the radioimmunoassays for glucagon-like peptide-2 (PG 126-159) and for PG 151-158, whereas the assay for PG 151-160 was completely negative. We conclude that the C-terminal amino acid residue of pig and human ileal GLP-2 is PG 158. Thus the basic residues, PG 159 and 160 are removed during its processing in the small intestine.

In pneumococcal meningitis a novel water-soluble inhibitor of matrix metalloproteinases and TNF-alpha converting enzyme attenuates seizures and injury of the cerebral cortex.

Matrix metalloproteinases (MMPs) and TNF-alpha converting enzyme (TACE) contribute to the pathophysiology of bacterial meningitis. To date, MMP-inhibitors studied in models of meningitis were compromised by their hydrophobic nature. We investigated the pharmacokinetics and the effect of TNF484, a water-soluble hydroxamate-based inhibitor of MMP and TACE, on disease parameters and brain damage in a neonatal rat model of pneumococcal meningitis. At 1 mg/kg q6h TNF484 reduced soluble TNF-alpha and the collagen degradation product hydroxyproline in the cerebrospinal fluid. Clinically, TNF484 attenuated the incidence of seizures and was neuroprotective in the cortex. Water-soluble MMP-inhibitors may hold promise in the therapy of bacterial meningitis.

PreproPACAP-derived peptides occur in VIP-producing tumours and co-exist with VIP.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a newly discovered neuropeptide which exists in two biologically active forms: PACAP-38 consisting of 38 amino acids and PACAP-27, a peptide corresponding to the N-terminal 27 amino acids of PACAP-38. Both PACAPs are derived from a 176 amino acid precursor (preproPACAP) which in addition gives rise to a 29 amino acid peptide, designated PACAP-related peptide (PRP). The presence of the three preproPACAP-derived peptides (PACAP-38, PACAP-27 and PRP) in tumour tissue from nine patients with VIP-producing tumours (pancreatic carcinoma, neuroblastoma, ganglioneuroma and pheochromocytoma) and eleven patients with non-VIP-secreting tumours (gastrinoma, glucagonoma, somatostatinoma, neuroblastoma) was examined by specific radioimmunoassays. In seven out of the nine VIP-secreting tumours elevated concentrations of all the three preproPACAP-derived peptides were found compared with normal tissue, while the concentrations in the non-VIP-secreting tumours were within the normal range. PACAP-38 was in all cases the dominating peptide, the concentration ranging from 41 to 3606 pmol/g. When tumour extracts were fractionated on Sephadex G50 column, tricine gel electrophoresis or reverse-phase HPLC immunoreactive components corresponding to synthetic PACAP-38, PACAP-27 and human PRP were identified, suggesting that preproPACAP was fully processed. Immunocytochemical examination showed PACAP-immunoreactive cells in the tumour tissue which also stained for VIP. This co-localization of PACAP and VIP was confirmed by double-staining experiments on the same sections, demonstrating PHM/VIP mRNA and PACAP-immunostaining in the same cells.

Effect of thyroid hormones on vasoactive intestinal polypeptide gene expression in the rat cerebral cortex and anterior pituitary.

We report here data on the expression of the various sequences derived from the prepro-vasoactive intestinal polypeptide (VIP) precursor and VIP mRNA in the anterior pituitary gland and cerebral cortex of hypothyroid and hyperthyroid rats. Using specific antisera to each of the prepro-VIP sequences we demonstrated an increase of all prepro-VIP derived sequences, and accordingly, found that the number of cells expressing each of these sequences were markedly augmented in the anterior pituitary of the hypothyroid rats. This was accompanied by a marked increase in VIP mRNA. In the cerebral cortex of the hypothyroid rats no changes were observed. In the pituitary of hyperthyroid animals a significant decrease was seen for prepro-VIP 22-79, VIP and prepro-VIP 156-170, whereas in the cerebral cortex a significant increase was observed for prepro-VIP 22-79, PHI and VIP. We were not able to demonstrate any changes in VIP mRNA in the cerebral cortex or pituitary of the hyperthyroid rats. Gel permeation chromatography and reverse-phase HPLC of extracts from cerebral cortex showed elution profiles identical to the synthetic counterparts. The reported data provide further evidence of a tissue-specific expression and regulation of the VIP gene products.

Expression of prepro-VIP derived peptides in the gastrointestinal tract of normal, hypothyroid and hyperthyroid rats.

Vasoactive intestinal polypeptide (VIP) is a widespread neuropeptide involved in the autonomic nervous control of smooth muscle activity, blood flow and secretion. To study the biosynthetic processing of the VIP precursor in the gut of normal, hypo- and hyperthyroid rats we used antisera against the five functional domains of the precursor molecule, prepro-VIP 22-79, peptide histidine isoleucine (PHI), prepro-VIP 111-122, VIP and prepro-VIP 156-170, to quantify and characterize VIP precursor peptides by radioimmunoassay and chromatography and examine their cellular localization and co-localization by immunohistochemistry. All five peptides were expressed in the gut but not in equimolar amounts as expected from the structure of the VIP precursor. A high concentration of PHV, the C-terminally extended form of PHI which includes prepro-VIP 111-122, was found in the small intestine. Immunohistochemically the prepro-VIP derived peptides were shown to coexist in neuronal elements. Changes in thyroid hormone status induced moderate changes in peptide expression in the gut, the most prominent being a 2-fold increase in all prepro-VIP derived peptides in the gastric fundus of hypothyroid rats. The findings indicate that differences in the post-translational processing of prepro-VIP exist in neurons of the rat gut and that hypo- and hyperthyroidism induce differential changes in peptide expression.

Cardiac vein myocardial revascularization. An experimental study and report of 3 clinical cases.

The feasibility of utilizing the coronary venous system for myocardial revascularization was explored in 18 dog experiments and 3 clinical patients at St. Mary Medical Center. Experimental models were developed using mammary artery-to-coronary vein anastomoses, free vein grafts from the aorta to the coronary veins, and saphenous vein bypass grafts from the aorta to the cardiac veins in the patients. Evaluation of myocardial revascularization was done by one or more of the following methods: (1) electromagnetic flowmeter measurements of graft blood flow; (2) myocardial scanning after injection of radioactive materials; (3) hydrogen electrode evaluation of arteriovenous shunting; (4) coronary cineangiograms; (5) methylene blue injections with visual observation of myocardial staining and collateral venous pathways; (6) pulse-flow tracings; (7) electrocardiographic changes; and (8) myocardial venous capillary response to papaverine and isoproterenol. The experimental studies consistently demonstrated evidence of myocardial revascularization through the coronary venous system. Three patients with intractable angina pectoris and previous unsuccessful revascularization procedures underwent saphenous vein bypass grafting from the aorta to the coronary vein. Postoperative coronary cineangiograms showed patency in 2 of 4 grafts. Myocardial scanning demonstrated radioactivity in the regions served by the patent grafts. All patients survived and were partially or completely relieved of their symptoms.