Carnegie Mellon University's MMM program: management education for 21st-century physicians.

The number and types of executive and graduate-level management programs for physicians have exploded in recent years. These programs take on a variety of formats, ranging from executive seminars to master's-level degree programs. Options for physicians obtaining the master's degree tend to be either regionally based programs in traditional evening classes or nationally based programs that combine executive education formats with distance education. This paper examines a nationally based program - the Master of Medical Management (MMM) - from the perspectives of an administrator and a graduate of the program. It offers reasons for the growth of similar programs and data from students enrolled in the Carnegie Mellon University MMM program. The paper also examines educational outcomes in the form of behavioral competencies that the physicians acquired in the program. It concludes with reflections on the future of the MMM and related programs for physician executives in the 21st century.

Acantholytic epidermolysis bullosa.

BACKGROUND: We describe a new variant of inherited epidermolysis bullosa and elucidate the clinical, histologic, and ultrastructural features of this condition. OBSERVATIONS: This form of epidermolysis bullosa displays an autosomal dominant inheritance pattern, is characterized by acral bullae, and histologically demonstrates suprabasal clefting with acantholysis. Ultrastructural findings are nonspecific but reminiscent of those observed in benign familial pemphigus. CONCLUSION: Acantholytic epidermolysis bullosa is a rare but distinct clinicopathologic entity that warrants inclusion in the nosologic classification of epidermolysis bullosa.

Papular mucinosis in L-tryptophan-induced eosinophilia-myalgia syndrome.

Five patients with the L-tryptophan-related eosinophilia-myalgia syndrome had a generalized eruption of flesh-colored papules. In all patients, histologic examination revealed a focal accumulation of mucin in the upper mid dermis, associated with increased dermal cellularity. The mucin was composed predominantly of hyaluronic acid, with small amounts of sulfated acid mucopolysaccharides. The cells within the lesion were fibroblasts. The lesions slowly regressed after L-tryptophan was discontinued. Proposed explanations for the L-tryptophan-related eosinophilia-myalgia syndrome have centered on contaminants, chemically related to L-tryptophan, introduced in the manufacturing process. Tryptophan metabolites have been linked with sclerotic cutaneous diseases but have not been previously implicated in cutaneous mucinoses.

Caseating cutaneous granulomas in a patient with X-linked infantile hypogammaglobulinemia.

A 34-year-old man with X-linked infantile hypogammaglobulinemia, bronchiectasis, and chronic liver disease had a papular eruption on the trunk and upper extremities. A biopsy specimen revealed caseating granulomas, but special stains, cultures, and electron microscopy failed to reveal an infectious organism. Immunohistochemistry showed that the lymphocytes within the granulomas were almost exclusively of the CD8+ cytotoxic/suppressor T phenotype. Phenotypic analysis of the circulating lymphocytes showed normal numbers of CD4+ (helper/inducer) and CD8+ T cells, whereas B cells were undetectable. Other examples of noninfectious granulomatous disease have been reported in patients with primary hypogammaglobulinemia, but this is the first case of caseating cutaneous granulomatous disease to be reported in a patient with X-linked infantile hypogammaglobulinemia.

Abnormal elastic tissue in cartilage-hair hypoplasia.

A 29-year-old white woman had short limbs, hyperextendable joints, fine skin and body hair, anergy to common skin test antigens, subnormal lymphocyte response to phytohemagglutinin, and increased numbers of natural killer cells, characteristic of cartilage-hair hypoplasia, an autosomal, recessively inherited disorder found in America mainly among the old-order Amish. Her forearm skin was hyperextendable and numerous verrucae were present on the digits of her hands. A skin biopsy from hyperextendable skin showed ovoid, 10- to 20-micron bodies in the papillary dermis. Ultrastructurally, the bodies were interpreted as abnormal elastic fibers.

Clinicopathologic types of epidermolysis bullosa and their nondermatological complications.

The various epidermolysis bullosa syndromes are classified into (1) epidermolytic, (2) lamina lucidolytic (junctional), and (3) dermolytic (dystrophic) subgroups. The mode of inheritance and the clinical manifestations, both cutaneous and noncutaneous, are systematically summarized. This report provides an overview of the diverse epidermolysis bullosa syndromes, particularly from the perspective of their nondermatological manifestations.

Dermolytic (dystrophic) epidermolysis bullosa inversa.

We treated four patients with an inverse form of recessive dermolytic (dystrophic) epidermolysis bullosa. The distinguishing features of the disease are (1) early generalized skin involvement with blisters and erosions that heal with superficial, atrophic scars; (2) persistence into adulthood, although milder; (3) severity in flexural areas, especially the inguinal folds, perineum, axillae, submammary area, posterior and lateral aspects of the neck, and often the lower parts of the abdomen and back; (4) normal stature and general development; (5) severe oral and esophageal mucosal involvement; (6) normal teeth; (7) normal or minimally involved fingernails, but mild to moderately dystrophic or atrophic toenail changes; and (8) microscopic findings similar to those of the Hallopeau-Siemens form of epidermolysis bullosa.

The generalized atrophic benign form of junctional epidermolysis bullosa. Experience with four patients in the United States.

We encountered four patients in the United States with the generalized atrophic benign form of junctional epidermolysis bullosa (epidermolysis bullosa atrophicans generalisata mitis, nonlethal junctional epidermolysis bullosa). Prior to the performance of definitive diagnostic studies, each patient had been thought for at least a decade to have either a dystrophic or simplex form of epidermolysis bullosa. Each patient had generalized blisters since birth that healed with atrophy and mild scarring but without milia or contractures. Two of the four patients had experienced laryngeal involvement during childhood. In each patient, correct diagnosis was finally established by either electron microscopic examination or immunofluorescence mapping of skin sections from induced blisters.

Elastase and neutral cathepsin production by human fibroblasts: effect of culture conditions on synthesis and secretion.

Fibroblasts from normal adult forearm skin and neonatal foreskin were cultured and examined for their ability to synthesize and secrete elastase and neutral cathepsin. All of the cultures examined produced detectable amounts of elastase using insoluble elastin as substrate. An enzyme was also found that hydrolyzed the synthetic elastin substrate, N-succinyl-(Ala)3-p-nitroanilide, but did not degrade insoluble elastin. In addition, activity against the synthetic cathepsin substrate N-benzoyl-DL-phenylalanine-naphthyl ester was found. Inhibitor profiles indicate that the elastin and N-succinyl-(Ala)3-p-nitroanilide degrading activities are due to metalloproteinases. Degradation of N-benzoyl-DL-phenylalanine-naphthyl ester can be inhibited by phenylmethylsulfonyl fluoride. These proteinases were usually found associated with the cell layer. Although activities of the measured proteinases were detected in all cultures, increased or decreased enzyme activities were not predictably related to passage number or length of serum starvation. Degree of confluence also affected proteinase activities. Separation of the dermal-epidermal junction can be produced by the injection of these proteinases into intact mouse skin.

Nalidixic acid-induced photosensitivity in mice: a model for pseudoporphyria.

Porphyria cutanea tarda (PCT)-like photosensitivity eruptions have occurred in patients treated with nalidixic acid, furosemide (Lasix), or tetracycline. An animal model for nalidixic acid photosensitivity was developed in young CF-1 female mice. The hair on the back was plucked from groups of animals that were injected i.p. each day with nalidixic acid or saline. The animals were exposed to black-lamp radiation for 12 h daily for 6 weeks, followed by a 2-week rest period, and then 4 more weeks of UV radiation exposure. The nalidixic acid-treated animals developed far greater gross and chronic inflammatory changes than the saline-treated animals; microscopically and ultrastructurally they showed blister formation beneath the basal lamina at the same level as that found in PCT. This model appears to be suitable for the study of PCT-like and other photosensitivity reactions.

Progressive vaccinia associated with combined variable immunodeficiency.

Progressive vaccinia developed in a previously healthy woman following smallpox vaccination and was successfully treated with vaccinia immune human globulin and methisazone. Immunologic evaluation over the next 4 1/2 years revealed evidence for combined variable immunodeficiency with increased numbers of circulating OKT 8 positive (suppressor-cytotoxic T) cells and the virtual absence of OKT 4 positive (helper-inducer T) cells.

Factor XI assay results in the CAP survey (1981).

Data from the 1981 CAP Survey for factor XI assay is reviewed. Different instrument reagent combinations are ranked according to precision and sensitivity. Results of the survey questionnaire are analyzed. There is poor correlation between precision and sensitivity of most systems (i.e., instrument and reagent combinations). For any given system, precision appears to decrease with increasing severity of the factor XI deficiency of the specimen. Some comparisons are made to recent CAP surveys of factor VIII and IX activity. Considerable interlaboratory variation is noted with respect to technical aspects of factor assays (i.e., dilution of normal plasma used to construct the standard curve, etc.). Procedures used by some laboratories in handling patient specimens for factor assays, such as freezing the patient specimen, may decrease the chance of identifying a mild factor XI deficiency. The need for standardization of factor assays is evident from the survey data.