Cancer diagnosis and telemedicine: a case study from Cambodia.

Cambodia is one of the least developed countries in the world, and presents major challenges to the provision of effective healthcare. Partners Telemedicine, a non-profit organization based in Boston, MA, is leading a pilot project to assess whether accurate diagnosis and treatment can be provided by email to patients in remote locales in the developing world. This project, in rural Cambodia, has had a beneficial impact on the public health of the communities served. There has been a reduced demand for acute care services, with patients seeking treatment earlier and adhering better to their prescribed treatment regimens for chronic diseases, and the project illustrates the potential for simple communications technology to improve care, even to some of the most impoverished communities. However, infrastructure must be improved in Cambodia to enable patients, in particular cancer patients, to receive acute care that can only be provided in distant Phnom Penh.

Role for telemedicine in acute stroke. Feasibility and reliability of remote administration of the NIH stroke scale.

BACKGROUND AND PURPOSE: Immediate access to physicians experienced in acute stroke treatment may improve clinical outcomes in patients with acute stroke. Interactive telemedicine can make stroke specialists available to assist in the evaluation of patients at multiple urban or remote rural facilities. We tested whether interrater agreement for the NIH Stroke Scale (NIHSS), a critical component of acute stroke assessment, would persist if performed over a telemedicine link. METHODS: One bedside and 1 remote NIHSS score were independently obtained on each of 20 patients with ischemic stroke. The bedside examination was performed by a stroke neurologist at the patient's bedside. The remote examination was performed by a second stroke neurologist through an interactive high-speed audio-video link, assisted by a nurse at the patient's bedside. Kappa coefficients were calculated for concordance between bedside and remote scores. RESULTS: Remote assessments took slightly longer than bedside assessments (mean 9.70 versus 6.55 minutes, P<0. 001). NIHSS scores ranged from 1 through 24. Based on weighted kappa coefficients, 4 items (orientation, motor arm, motor leg, and neglect) displayed excellent agreement, 6 items (language, dysarthria, sensation, visual fields, facial palsy, and gaze) displayed good agreement, and 2 items (commands and ataxia) displayed poor agreement. Total NIHSS scores obtained by bedside and remote methods were strongly correlated (r=0.97, P<0.001). CONCLUSIONS: The NIH Stroke Scale remains a swift and reliable clinical instrument when used over interactive video. Application of this technology can bring stroke expertise to the bedside, regardless of patient location.

Syringolymphoid hyperplasia and follicular mucinosis in a patient with cutaneous T-cell lymphoma.

Syringolymphoid hyperplasia with alopecia is an uncommon chronic dermatosis of which 9 cases have been reported, with or without follicular mucinosis or cutaneous T-cell lymphoma. We report a patient with cutaneous T-cell lymphoma and syringolymphoid hyperplasia and follicular mucinosis and review the previously reported cases. All reported cases with syringolymphoid hyperplasia were men (10 of 10), with the clinical findings of alopecia (9 of 10) and anhidrosis (3 of 10). Only 3 of 10 cases had associated follicular mucinosis. Of the 7 cases investigated, 6 were found to hve cutaneous T-cell lymphoma. Three patients were not investigated for cutaneous T-cell lymphoma. Although syringolymphoid hyperplasia can be idiopathic, it can also reflect a syringotropic cutaneous T-cell lymphoma. Careful follow-up with a biopsy of persistent lesions is recommended to evaluate for the presence of lymphoma.

Electronic home monitoring of congestive heart failure patients: design and feasibility.

The efficacy of electronic monitoring in the home care of heart failure (HF) patients has not been widely reported. We developed a Vital Sign System (VSS) monitoring device capable of measuring the weight, blood pressure, and heart rate of congestive heart failure (CHF) patients in the home and transmitting these measurements via modem to a World Wide Web server. In this study of 22 CHF patients, we tested the reliability of the VSS electronic measurements compared to manual measurements taken by visiting home care nurses and ease of use of the VSS units as rated by both patients and home care nurses. The correlation of electronic to manual measurements was high (weight r=0.99; systolic blood pressure [SBP] r=0.84; diastolic blood pressure [DBP] r=0.54; heart rate [HR] r=0.88). The mean difference between electronic and manual measurements was within an acceptable range for clinical surveillance and care of CHF patients (weight 1.6 lbs; SBP 8.8 mm Hg; DBP 9.2 mm Hg; HR 0.7 bpm) The devices were rated favorably by both nurses and patients. The VSS monitoring device is a reliable, feasible, and favorably rated technology for home surveillance of CHF patients. (c)1999 by CHF, Inc.

Teledermatology in a capitated delivery system using distributed information architecture: design and development.

OBJECTIVE: This report describes the design, development, and technical evaluation of a teledermatology system utilizing digital images and electronic forms captured through, stored on, and viewed through a common web server in an urban capitated delivery system. MATERIALS AND METHODS: The authors designed a system whereby a primary care physician was able to seek a dermatologic consultation electronically, provide the specialist with digital images acquired according to a standardized protocol, and review the specialist response within 2 business days of the request. The settings were two primary care practices in eastern Massachusetts that were affiliated with a large integrated delivery system. Technical evaluation of the effectiveness of the system involved 18 patients. Main outcome measures included physician and patient satisfaction and comfort and efficiency of care delivery. RESULTS: In 15 cases, the consultant dermatologist was comfortable in providing definitive diagnosis and treatment recommendations. In 3 cases, additional information (laboratory studies or more history) was requested. There were no instances where the dermatologist felt that a face-to-face visit was necessary. CONCLUSIONS: This novel approach shows promise for the delivery of specialist expertise via the internet. Cost-effectiveness studies may be necessary for more widespread implementation.

Telemedicine in vascular surgery: feasibility of digital imaging for remote management of wounds.

PURPOSE: Telemedicine coupled with digital photography could potentially improve the quality of outpatient wound care and decrease medical cost by allowing home care nurses to electronically transmit images of patients' wounds to treating surgeons. To determine the feasibility of this technology, we compared bedside wound examination by onsite surgeons with viewing digital images of wounds by remote surgeons. METHODS: Over 6 weeks, 38 wounds in 24 inpatients were photographed with a Kodak DC50 digital camera (resolution 756 x 504 pixels/in2). Agreements regarding wound description (edema, erythema, cellulitis, necrosis, gangrene, ischemia, and granulation) and wound management (presence of healing problems, need for emergent evaluation, need for antibiotics, and need for hospitalization) were calculated among onsite surgeons and between onsite and remote surgeons. Sensitivity and specificity of remote wound diagnosis compared with bedside examination were calculated. Potential correlates of agreement, level of surgical training, certainty of diagnosis, and wound type were evaluated by multivariate analysis. RESULTS: Agreement between onsite and remote surgeons (66% to 95% for wound description and 64% to 95% for wound management) matched agreement among onsite surgeons (64% to 85% for wound description and 63% to 91% for wound management). Moreover, when onsite agreement was low (i.e., 64% for erythema) agreement between onsite and remote surgeons was similarly low (i.e., 66% for erythema). Sensitivity of remote diagnosis ranged from 78% (gangrene) to 98% (presence of wound healing problem), whereas specificity ranged from 27% (erythema) to 100% (ischemia). Agreement was influenced by wound type (p < 0.01) but not by certainty of diagnosis (p > 0.01) or level of surgical training (p > 0.01). CONCLUSIONS: Wound evaluation on the basis of viewing digital images is comparable with standard wound examination and renders similar diagnoses and treatment in the majority of cases. Digital imaging for remote wound management is feasible and holds significant promise for improving outpatient vascular wound care.

Telemedicine. Present applications and future prospects.

Information technology has enabled much of the business community to function in a time and place-independent manner. Health care has lagged in adopting this technology because of tradition, concern for patient security and confidentiality, liability, and licensure issues. This article reviews the current state of telemedicine technology, its applications, and opportunities for further development. Urology is identified as a specialty that stands to benefit from advances in technologies applicable to remote diagnosis, monitoring and care of patients, physician training, and record keeping.

The substitution of digital images for dermatologic physical examination.

OBJECTIVE: To investigate the diagnostic accuracy of clinicians viewing a patient's history and static digital image set compared with clinicians who conducted office-based physical examinations of the same patients. DESIGN: Observational study. SETTING AND PATIENTS: One hundred sixteen adult patients presenting with dermatologic symptoms in a university-based practice who consented to have their skin conditions documented with a still digital camera according to a standardized protocol. MAIN OUTCOME MEASURES: Concordance between office-based dermatologists' diagnoses and 2 remote clinicians' diagnoses using still digital images (resolution, 92 dots per inch) and identical medical history data to render diagnoses. RESULTS: When photographic quality was high and office-based clinician certainty was high, remote clinicians were in agreement more than 75% of the time. Office-based and remote clinicians were in agreement 61% to 64% of the time for all cases. No specific disease category appeared to be more or less amenable to diagnosis based on still digital imagery. The diagnostic certainty of the office-based clinician (reported from 0-10) had the most impact on agreement. When cases with office-based clinician certainty of no more than 7 were compared with cases with certainty of at least 9, agreement increased 54% for remote clinician 1 and 111% for remote clinician 2. As an isolated variable, photographic quality had a modest impact on agreement. CONCLUSIONS: Still digital images can substitute for the dermatologic physical examination in up to 83% of cases. This study provides validation of the store-and-forward concept of telemedicine as applied to dermatology. These results serve as the foundation for field testing of the concept in primary care settings.

Loose anagen syndrome and loose anagen hair.

Loose anagen syndrome, or loose anagen hair, is a recently described condition of unknown etiology that may be under-recognized. The typical patient is a child with sparse fine hair that can easily be pulled out. The diagnosis is confirmed by microscopic examination of firmly pulled hairs, many of which are in the anagen phase but lacking an inner and outer root sheath and demonstrating a ruffled cuticle. Some presentations of alopecia areata may be confused with this condition, but the pull test analysis serves to differentiate them. A variety of theories have been postulated to explain the pathophysiology of loose anagen syndrome. In some cases, there is an autosomal dominant pattern of inheritance. In most cases, this condition spontaneously improves with age.

The pancornulins: a group of small proline rich-related cornified envelope precursors with bifunctional capabilities in isopeptide bond formation.

In this report, the pancornulins are identified as members of the spr (small, proline-rich) multigene family by amino acid sequence and mass spectrometry analyses. One of the pancornulins (14.9 kDa) is identical to the protein predicted by spr-1 clone 128. The other pancornulins (16.9 kDa and 22 kDa) are novel members of the spr family. Immunoelectron microscopy of purified cornified envelopes with a pancornulin-specific antibody established these proteins more definitively as cornified envelope precursors. In addition, two-dimensional electrophoretic analyses of keratinocyte extracts labeled enzymatically with dansylcadaverine (to identify amine acceptors) or dansylPGGQQIV (to identify amine donors) showed that both glutamine and lysine residues within the pancornulins participate in the isopeptide linkage characteristic of cornified envelope formation. These results contrasted with those obtained using involucrin, a prominent cornified envelope protein shown capable of acting only as an amine acceptor in this system. Novel partial cDNAs obtained after reverse transcription and polymerase chain reaction amplification of total messenger RNA with pancornulin-specific primers suggest that the spr multigene family may be even larger than previously described. The bifunctional reactivity of the pancornulins in cross-linking and the large number of family members identified to date suggest that the pancornulins and other spr-1-related proteins may be more important in cornified envelope formation than previously considered, perhaps functioning as "bridge" molecules during the early phases of cornified envelope assembly.

Teledermatology in a changing health care environment.

To avoid marginalization and an attendant decline in the quality of care delivered, dermatologists must take the lead in defining those services that can be delivered remotely and move aggressively to create standards of nomenclature, protocols for imaging, and methods of care delivery that can be implemented in a primary-care setting. Because of the rigorous training of its practitioners in visual analysis, it may be possible for dermatology to shift from its traditional face-to-face model to an image-based, remotely practiced one. Transition to remote practice may even be critical to the survival of the specialty. Chief among the issues in the implementation of teledermatology is whether the use of video conferencing or store-and-forward technology provides the most efficient, high-quality remote diagnosis. Ancillary issues, including image protocols, bandwidth requirements, reimbursement, licensing, liability, and patient and provider satisfaction, are important as well. These issues are discussed in a framework of capitated payment in urban, integrated delivery systems. Teledermatology has many challenges to meet before competing with face-to-face delivery of dermatologic care.

Binding of keratin intermediate filaments (K10) to the cornified envelope in mouse epidermis: implications for barrier function.

The cornified envelope, a structure unique to keratinocytes, is a hallmark of their terminal differentiation and plays an important role in epidermal barrier function. Cornified envelope is formed through the action of a membrane-associated transglutaminase, which covalently cross-links protein precursors into a highly insoluble network at the inner leaflet of the plasma membrane in granular keratinocytes and stratum corneum. Initial studies, using dansylcadaverine for enzyme-directed labeling of acyl-acceptor transglutaminase substrates in mouse epidermal homogenates identified a prominent 60-kDa substrate. Specific antibodies raised to this protein stained the cytoplasm of suprabasal cells of stratified squamous epithelia, whereas simple epithelia and nonepithelial tissues showed no staining. Immunoscreening of a cDNA expression library from adult mouse skin identified 18 positive clones. DNA sequencing of the largest clone (which hybridized to a keratinocyte-specific transcript of 2.0 kb) showed greater than 99.5% homology with mouse keratin 10. Immunoelectron microscopy using anti-S60 and another antibody to keratin 10 showed specific binding to cornified envelope associated filamentous structures. Proteolytic fragments of purified cornified envelope from mouse epidermis showed reactivity to anti-S60. These data show that mouse keratin 10 is tightly bound to cornified envelope and may be a cross-linked substrate. The tight binding of keratin filaments and CE suggests a mechanism by which they might interact to enhance the structural integrity of the stratum corneum.

Epithelial cornified envelope precursors are in the hair follicle and nail.

Nail and certain layers of the hair follicle form cornified envelopes (CEs) that morphologically resemble those in epidermis. We have been studying two unique precursors of the CE in human epidermis, pancornulin and sciellin. Antibodies to these proteins stained the more central cells of the outer root sheath of the ostium and isthmus of the follicle where CEs are found. Staining was also observed with these antibodies in the inner root sheath, where CEs were thought not to be present. Using immunoelectron microscopy, the staining by the sciellin antibody was at the cell periphery, but this technique did not work with the antibody to pancornulin. The antibody to pancornulin reacted to the nail fold and proximal matrix, whereas the one to sciellin reacted with the nail fold, matrix, and bed. Similar reactions were observed to monkey, sheep, and cow nail. These results suggest that envelope precursor may have an additional function in the hair follicle as well as contributing to the CE in hair and nail.

Loose anagen hair as a cause of hereditary hair loss in children.

BACKGROUND AND DESIGN: The loose anagen hair syndrome is a recently described disorder with enhanced hair loss in which anagen hairs can be painlessly pulled from the scalp. RESULTS: In three families, we have observed an autosomal dominant form of inheritance. We have confirmed that the extracted bulbs consist only of cortical cells and that the hair shafts have an abnormal shape. Using routine light and electron microscopy, we observed disadhesion between all layers of the follicle and within some layers and premature keratinization of the inner root sheath of the follicle. In addition, abnormal maturation of the various layers was observed at the electron microscopic level, including regions of the cortex that contained decreased numbers of filaments. The disorder appears to be cyclic, since relatively normal and markedly affected regions of the shaft can be observed within a single follicle. CONCLUSIONS: Possible mechanisms responsible for the disease include abnormal intercellular signaling and disturbances of desmosomal components and/or cadherins.

Characterization of sciellin, a precursor to the cornified envelope of human keratinocytes.

The cornified envelope, located beneath the plasma membrane of terminally differentiated keratinocytes, is formed as protein precursors are cross-linked by a membrane associated transglutaminase. This report characterizes a new precursor to the cornified envelope. A monoclonal antibody derived from mice immunized with cornified envelopes of human cultured keratinocytes stained the periphery of more differentiated cells in epidermis and other stratified squamous epithelia including hair and nails. The epitope was widely conserved among mammals as determined by immunohistochemical and Western analysis. Immunoelectron microscopy localized the epitope to the cell periphery in the upper stratum spinosum and granulosum of epidermis. In the hair follicle, the epitope was present in the internal root sheath and in the infundibulum, the innermost aspect of the external root sheath. The antibody recognized a protein of relative mobility (M(r)) 82,000, pI 7.8. The protein was a transglutaminase substrate as shown by a dansylcadaverine incorporation assay. Purified cornified envelopes absorbed the reactivity of the antibody to the partially purified protein and cleavage of envelopes by cyanogen bromide resulted in release of immunoreactive fragments. The protein was soluble only in denaturing buffers such as 8 M urea or 2% sodium dodecyl-sulfate (SDS). Partial solubility could be achieved in 50 mM TRIS pH 8.3 plus 0.3 M NaCl (high salt buffer); the presence of a reducing agent did not affect solubility. Extraction of cultured keratinocytes in 8 M urea and subsequent dialysis against 50 mM TRIS pH 8.3 buffer resulted in precipitation of the protein with the keratin filaments. Dialysis against high salt buffer prevented precipitation of the protein. The unique solubility properties of this protein suggest that it aggregates with itself and/or with keratin filaments. The possible role of the protein in cornified envelope assembly is discussed. We have named this protein Sciellin (from the old english "sciell" for shell).

Keratinocytes stimulate prostaglandin I2 synthesis by 3T3 cells and exhibit enhanced cornification when exposed to prostaglandin I2 analogues.

The predominant cyclooxygenase products of keratinocytes are prostaglandin (PG)E2 and PGF2 alpha with only trace amounts of PGI2 synthesis detected. When normal or immortal (NM1) keratinocytes were co-cultured with mitomycin C-treated 3T3 cells, increased synthesis of PGI2 was noted compared to mitomycin C-treated 3T3 cells alone. The PGI2 level in co-cultures was maximum within the first week and diminished rapidly thereafter. These results suggested keratinocytes enhance the production of PGI2 by 3T3 cells. Keratinocyte cultures incubated with Iloprost and Piriprost, stable PGI2 analogues, showed evidence of increased cornification as demonstrated by staining with rhodanile blue, decreased shedding of cells into the culture medium, and more cornified material adhering to the culture surface. The cultures appeared to be responsive between the first and second weeks after plating and the inhibition of shedding could not be reversed by changing to drug-free medium. Control and treated cultures showed identical electrophoretic protein patterns. Immunoblots showed involucrin unchanged in extracts of control and treated cultures while the 22 kd pancornulin was absent in treated cultures. The findings that keratinocytes enhance the production of PGI2 by 3T3 cells and that PGI2 analogues enhance cornification of confluent keratinocytes raise the possibility that eicosanoids may serve as autoregulatory signals together with other factors.

Detection of substrates of keratinocyte transglutaminase in vitro and in vivo using a monoclonal antibody to dansylcadaverine.

A method providing more sensitive detection of transglutaminase substrates was developed to localize transglutaminase activity in tissue and to identify in vivo substrates in epidermal extracts. The enhanced sensitivity of this method was achieved via the generation of a monoclonal antibody (designated E7) made to dansylcadaverine. Transglutaminase substrates were visualized by western blot after a 1-min incubation with dansylcadaverine in contrast to the 2 h required when [14C]putrescine incorporation was measured by autoradiography of SDS-polyacrylamide gels. In addition, putative substrates not apparent using conventional methods were readily detected by western analysis. An ELISA assay to measure transglutaminase activity showed similar sensitivity to the traditional radiometric assay (Lorand et al., 1972). The correlation between the ELISA procedure and the radiometric assay was high (r2 = 0.924). Strips of neonatal human and mouse skin incubated in dansylcadaverine-supplemented culture medium were used to localize enzyme activity and to detect substrates in vivo. Transglutaminase activity was demonstrated at the cellular periphery in the upper spinous and granular cell layers of the epidermis. Substrates detected in epidermal extracts were similar to those detected using the in vitro assay. This technique allows for highly sensitive and nonradiometric analysis of both enzymatic activity and the substrates involved. The extension of this methodology to an in vivo system is the first demonstration of a system in which the dynamics of cornified envelope assembly may be further studied.

Dietary management reverses grooving and abnormal polarization of hair shafts in argininosuccinase deficiency.

We have observed that the fragile hair of two untreated patients with argininosuccinic aciduria showed abnormal alternating zones of bright and dark banding by polarizing microscopy. Scanning electron microscopy documented discontinuous grooves with a 50 to 100 microns periodicity. Results of amino acid analysis of the hair were essentially normal. After the patients were treated with a low-protein, arginine-supplemented diet, the hair assumed a normal appearance. Five patients already treated with diet showed no hair abnormalities. The pathogenesis of the hair changes in unknown, but our findings suggest that products generated in the disease can adversely affect metabolically active tissue such as hair.