The Role of Mandated Research During Dermatology Residency Training (original) (raw)

are likely to represent preferred locations for base-pair exchanges rather than mutations derived from common ancestors.

The 53 DEB families were also tested for the presence of previously known common COL7A1 mutations in the exons 13,70,81,10413,70,81,104, and 116 by restriction enzyme digestion. These mutations were frequently found in either the Japanese ( S818delC,6573+1G→CS 818 \mathrm{delC}, 6573+1 \mathrm{G} \rightarrow \mathrm{C}, E2843X) 3{ }^{3} or the British population (R578X, 7786delG; Mellerio et al, 1997). Only one DEB inversa patient in our collective was a heterozygous carrier of the substitution R578X in exon 13, indicating that these mutations are not common in a Central-European population.

In summary, in this study we identified a missense mutation in exon 73 of COL7A1 in 28%28 \% of 53 unrelated DEB families. Addition of these gene defects to the previously published mutations yields a sum of 16 different gene defects in this exon of 201 bp . This large number of mutations, especially at some preferred nucleotide positions, suggests a gene region with high mutational frequency. Thus, it appears that exon 73 should be analyzed with priority by mutation screening of DEB patients. This knowledge is useful for accelerated mutation analysis of the COL7A1 gene, as well as for genetic counselling of DEB families with risk of recurrence.

The authors thank Margit Schubert and Michaela Floeth for expert assistance and Dr. Alain Hovnanian and Dr. Anaraj Sakuntabhai for help with the Southern blot analysis. The authors’ work was supported by grants Br 1475/1-2 and 2-3 from the Deutsche Forschungsgemeinschaft, by the EU contract Nr. BMH-4-97-2339 and by DEBRA U.K.

Sabine Mecklenbeck, Nadja Hammami-Hausali, Bianca Höpfner, Hauke Schumann, Annika Kramer, Wolfgang Küster,* Leena Bruckner-Tuderman Department of Dermatology, University of Münster, Münster, Germany
*TOMESA Clinic, Bad Salzschlirf, Germany

REFERENCES

Burgeson RE: Type VII collagen, anchoring fibrils, and epidermolysis bullosa. J Invest Dermatol 101:252-255, 1993

Christiano AM, Ryynänen M, Uitto J: Dominant dystrophic epidermolysis bullosa: Identification of a Gly-4Ser substitution in the triple helical domain of type VII collagen. Proc Natl Acad Sci USA 91:3549-3553, 1994
Christiano AM, Morricone A, Paradisi M, Angelo C, Mazzanti C, Cavalieri R, Uitto J: A glycine-to-arginine substitution in the triple helical domain of type VII collagen in a family with dominant dystrophic epidermolysis bullosa. J Invest Dermatol 104:438-440, 1995
Christiano AM, McGrath JA, Uitto J: Influence of the second COL7A1 mutation in determining the phenotypic severity of recessive dystrophic epidermolysis bullosa. J Invest Dermatol 106:766-770, 1996a
Christiano AM, Bart BJ, Epstein EH, Uitto J: Genetic basis of Bart’s syndrome: a glycine substitution mutation in the type VII collagen gene. J Invest Dermatol 106:1340-1342, 1996b
Christiano AM, Hoffman GG, Zhang X, Xu Y, Tamai Y, Greenspan DS, Uitto J: Strategy for identification of sequence variations in COL7A1, and a novel 2bp deletion mutation in recessive dystrophic epidermolysis bullosa. Hum Mutat 10:408-414, 1997
Cierfudni-Friedman PB, Karpati S, Horvath A, Christiano AM: Identification of the glycine to arginine substitution G2043R in the type VII collagen in a family with dominant dystrophic epidermolysis bullosa from Hungary. Exp Dermatol 6:303-307, 1997
Fine JD, Bauer EA, Briggaman RA, et al: Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa: consensus report by the subcommittee on diagnosis and classification of the National Epidermolysis Bullosa Registry. J Am Acad Dermatol 24:119-135, 1991
Hammami-Hausali N, Schumann H, Raghunath M, Kilgus O, Lüthi U, Luger T, Bruckner-Tuderman L: Some, but not all, glycine substitution mutations in COL7A1 result in intracellular accumulation of collagen VII, loss of anchoring fibrils, and skin blistering. J Biol Chem 272:19228-19234, 1998
Hovnanian S, Rochat A, Bodemer C, et al: Characterization of 18 new mutations in COL7A1 in recessive dystrophic epidermolysis bullosa provides evidence for distinct molecular mechanism underlying defective anchoring fibril formation. Am J Hum Genet 61:599-610, 1997
Järvikallio A, Pulkkinen L, Uitto J: Molecular basis of dystrophic epidermolysis bullosa: Mutations in the type VII collagen gene (COL7A1). Hum Mutat 10:338-347, 1997
Kon A, Pulkkinen L, Ishida-Yamamoto A, Hashimoto I, Uitto J: Novel COL7A1 mutations in dystrophic forms of epidermolysis bullosa. J Invest Dermatol 111:534-537, 1998
Mellerio JE, Dunhill MGS, Allison W, et al: Recurrent mutations in the type VII collagen gene (COL7A1) in patients with recessive dystrophic epidermolysis bullosa. J Invest Dermatol 109:246-249, 1997
Winberg JO, Hammami-Hausali N, Nilsson O, et al: Modulation of disease severity of dystrophic epidermolysis bullosa by a splice site mutation in combination with a missense mutation in the COL7A1 gene. Hum Mol Genet 6:11251135, 1997

The Role of Mandated Research During Dermatology Residency Training

To the Editor:

Dermatology residents at the University of Miami, Department of Dermatology and Cutaneous Surgery are required to complete a research project as part of their 3 y clinical training. We believe, as do programs in other specialties (Gupta, 1995; Alquire et al, 1996; Schultz, 1996), that research during residency training is a valuable educational tool. Some dermatology programs require residents to publish an article or case report as part of their training (Webb et al, 1996).

Each resident must submit a research grant proposal, by November of their first year, to a departmental research committee consisting of four faculty members. This committee assists residents in choosing, developing, and implementing a project and insures it is well formulated. Each resident must choose a mentor or faculty advisor, other research programs

[1]found a mentor to be positively associated with research productivity (Mills et al, 1995) and suggest that it may be the single most important component of a successful program (Eisenberg, 1986; Alquire et al, 1993).

The project may be either human based or laboratory based but should be controlled. Unlike other programs, case reports and literature reviews do not fulfill the research requirement. Initially some residents’ projects are too ambitious or lack appropriate controls. The research committee insures that the residents are on the right path, that their project is scientifically sound and can be completed during their training period, and that costs of completing a study are not unreasonable. Statistical consultation, for example, is a common need for most projects. Funding is provided by the advisor or by a departmental fund devoted to assist resident projects.

Projects involving human subjects or material need approval by our Institutional Review Board (IRB). Our department has in place support staff to assist residents with paper work associated with obtaining IRB approval. Residents often defend or discuss the proposal at the IRB meetings, which provide a valuable learning experience.

When implementing their projects, residents are encouraged

1. Manuscript received August 28, 1998; revised November 10, 1998; accepted for publication November 11, 1998.
   3{ }^{3} Dr. Robert Kirsner is recipient of the Dermatology Foundation’s Clinical Career Development Award in Health Care Policy. ↩︎

Table I. Journal names and number of articles published in each (N=148)(\mathbf{N}=148) (residents graduating from 1988 to 1995)

to act independently, although the research committee chairperson meets regularly with the residents. Residents present their plan before initiation as well as reporting interim and final results at our weekly scientific Research Meetings. Final results are presented at several forums including regional or national meetings, at our weekly scientific Research Meetings, and at the Miami Dermatological Society Annual Residents’ and Fellows’ Day.

Projects are not completed during any assigned “protected” time as the extent of protected time is often difficult to predict and may disrupt the overall residency schedule. Rather, residents undertake their research by either coming in early or staying late during the week, or alternatively on weekends.

One of the goals of the project is to submit a manuscript for publication and the majority of residents publish more than one ( 4.08±3.414.08 \pm 3.41 authorships per resident). Table I summarizes the journal these articles were published in. A survey of former residents found that although only a minority “liked” the research requirement during training, more than 50%50 \% believed research influenced the way they thought, the way they thought about patients, and how they treated patients, and 90%90 \% thought it was a beneficial part of their training (Table II).

We believe for select individuals, our research requirement prepares them for an academic career. Of 43 residents graduating from 1988 to 1995, eight became full time academicians, four remain so. For all, it develops their abilities as critical thinkers, and helps them to understand the methods and limitations of the research work upon which many clinical decisions rest.

Table II. Responses from resident (graduating years 198895); N=43\mathrm{N}=43 (response rate 71%)

Additionally, they learn the need for proper controls, the importance of reproducibility, the ethical issues important in research, and the vital role of statistics. Beyond reading about science in the Journal Club, the performance of research aids residents’ understanding of research’s benefits and limitations.

In the current health care environment, factors such as dermatologic research experience help separate dermatologists from others who care for skin disease. This level of preparation leads to higher quality research, not solely for those who make research a career, but for all dermatologists.

Robert S. Kirsner, 1∗{ }^{1 *} # Francisco A. Kerdel,* Vincent Falanga,* Jennifer Trent,* William H. Eaglstein* Departments of *Dermatology and Cutaneous Surgery and #Epidemiology and Public Health, University of Miami School of Medicine, Miami, Florida, U.S.A.

REFERENCES

Alquire PC, Anderson WA, Henry RC: Teaching research skills: development and evaluation of a new research program for residents. Teaching and Learning in Medicine 5:37-43, 1993
Alquire PC, Anderson WA, Albrecht RR, Poland GA: Resident research in Internal Medicine training programs. Ann Int Med 124:321-328, 1996
Eisenberg JM: Cultivating a new field: development of a research program in general internal medicine. J Gen Int Med I (Suppl. 4):S8-S18, 1986
Gupta G: Graduate Medical Education Directory 1995-96. Chicago: American Medical Association, 1995
Mills OF, Zyzanski SJ, Flocke S: Factors associated with research productivity in family practice residencies. Fam Med 27:188-193, 1995
Schultz HJ: Research during Internal Medicine residency training: Meeting the challenge of the residency review committee. Ann Int Med 124:340-342, 1996
Webb JM, Rye B, Fox L, et al: State of dermatology training. The residents’ perspective. J Am Acad Dermatol 34:1067-1071, 1996