Effect of reducing dietary forage in lower starch diets on performance, ruminal characteristics, and nutrient digestibility in lactating Holstein cows.

This experiment evaluated the effect of feeding a lower starch diet (21% of dry matter) with different amounts of forage (52, 47, 43, and 39% of dry matter) on lactational performance, chewing activity, ruminal fermentation and turnover, microbial N yield, and total-tract nutrient digestibility. Dietary forage consisted of a mixture of corn and haycrop silages, and as dietary forage content was reduced, chopped wheat straw (0-10% of dry matter) was added in an effort to maintain chewing activity. Dietary concentrate was adjusted (corn meal, nonforage fiber sources, and protein sources) to maintain similar amounts of starch and other carbohydrate and protein fractions among the diets. Sixteen lactating Holstein cows were used in replicated 4×4 Latin squares with 21-d periods. Dry matter intake increased while physically effective neutral detergent fiber (peNDF1.18) intake was reduced as forage content decreased from 52 to 39%. However, reducing dietary forage did not influence milk yield or composition, although we observed changes in dry matter intake. Time spent chewing, eating, and ruminating (expressed as minutes per day or as minutes per kilogram of NDF intake) were not affected by reducing dietary forage. However, addition of chopped wheat straw to the diets resulted in greater time spent chewing and eating per kilogram of peNDF1.18 consumed. Reducing dietary forage from 52 to 39% did not affect ruminal pH, ruminal digesta volume and mass, ruminal pool size of NDF or starch, ruminal digesta mat consistency, or microbial N yield. Ruminal acetate-to-propionate ratio was reduced, ruminal turnover rates of NDF and starch were greater, and total-tract digestibility of fiber diminished as dietary forage content decreased. Reducing the dietary forage content from 52 to 39% of dry matter, while increasing wheat straw inclusion to maintain chewing and rumen function, resulted in similar milk yield and composition although feed intake increased. With the lower starch diets in this short-term study, the minimal forage content to maintain lactational performance was between 39 and 43%.

Graft-versus-host disease in cyclosporin A-treated rats after syngeneic and autologous bone marrow reconstitution.

Lethally irradiated rats treated with cyclosporin A (CsA) for 20-40 d develop classic graft-versus-host disease (GVHD) when reconstituted with syngeneic or autologous bone marrow, upon discontinuation of CsA, whereas normal rats do not. Syngeneic GVHD may be transferred to irradiated but not normal syngeneic recipients. Normal spleen cells fail to prevent the development or adoptive transfer of syngeneic GVHD.

Epidermal HLA-DR and the enhancement of cutaneous reactivity to superantigenic toxins in psoriasis.

Streptococcal and staphylococcal superantigens (SAg's) have been implicated in the pathogenesis of inflammatory skin diseases, but the mechanisms by which these toxins act are unknown. The present study assessed the ability of nanogram quantities of topically applied purified toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin type B, and streptococcal pyrogenic enterotoxin types A and C to induce inflammatory reactions in clinically uninvolved skin of normal controls and subjects with psoriasis, atopic dermatitis, and lichen planus. These SAg's triggered a significantly greater inflammatory skin response in psoriatics than in normal control subjects or in subjects with atopic dermatitis or lichen planus. Surprisingly, skin biopsies did not exhibit the T-cell receptor Vbeta stimulatory properties predicted for SAg-induced skin reactions. By 6 hours after patch testing with SAg's, TNF-alpha mRNA had increased in the epidermis (but not the dermis) in biopsies from psoriatics, compared with controls. Immunohistochemical studies revealed significantly higher HLA-DR expression in keratinocytes from psoriatics than from controls. However, a mutant TSST-1 protein that fails to bind HLA-DR did not elicit an inflammatory skin reaction. These results indicate that keratinocyte expression of HLA-DR enhances inflammatory skin responses to SAg's. They may also account for previous studies failing to demonstrate selective expansion of T-cell receptor Vbetas in psoriatics colonized with SAg-producing Staphylococcus aureus, and they identify a novel T cell-independent mechanism by which SAg's contribute to the pathogenesis of inflammatory skin diseases.

UV radiation-induced tumors in haired mice: identification as squamous cell carcinomas.

The most common tumor induced by UV radiation in haired mice is considered to be a fibrosarcoma on the basis of its presentation as a nodule in the skin and on the basis of a spindled appearance upon light microscopic examination. A squamous cell carcinoma is thought to be a much less common tumor. In the present report this concept was reevaluated in mammary tumor virus-free C3H/HeNCr (C3H-) mice. From first appearance, almost all lesions upon gross morphologic examination have an epidermal component and initially are similar to solar keratoses in humans. The lesions then become nodular and eventually develop central ulceration, often with a rolled border characteristic of squamous cell carcinomas. The morphology upon light microscopic examination ranged from well-differentiated squamous cell carcinoma to a poorly differentiated spindle cell neoplasm. Occasionally, variable patterns of squamous differentiation were seen in the same lesion. Immunoperoxidase examination with a polyclonal antikeratin serum demonstrated the presence of keratin in 84 of 87 tumors. Frequent, poorly formed desmosomes were found on ultrastructural examination. These tumors usually had a regressor phenotype upon transplantation into recipients. In conclusion, almost all UV radiation-induced tumors in C3H- mice are squamous cell carcinomas, and these tumors are usually antigenic.

Development and field-test validation of an assay for DNA repair in circulating human lymphocytes.

A method for measuring nucleotide excision repair in response to UV irradiation and chemical-induced DNA damage has been developed, validated, and field tested in cultured human lymphocytes. The methodology is amenable to population-based screening and should facilitate future epidemiological studies seeking to investigate associations between DNA repair proficiency and cancer susceptibility. The impetus for such endeavors derives from the suggestion that the high incidence of skin cancer in the genetic disorder xeroderma pigmentosum is manifested as a result of the reduced capacity of patients' cells to repair DNA damaged by UV-mimetic agents. For the assay, damaged, nonreplicating, recombinant plasmid DNA harboring a chloramphenicol acetyltransferase (cat) reporter gene is introduced into lymphocytes by using a DEAE-dextran/DNA complex short-term transfection conditions. Excision repair of the damaged bacterial cat gene is monitored proportionately as a function of reactivated CAT enzyme activity following a 40-h repair/expression incubation period. The validity of the approach was indicated by the ability of the assay to discriminate xeroderma pigmentosum virus-transformed lymphocyte cell lines of both severe (complementation groups A and D) and moderate (complementation group C) excision repair deficiencies from repair-proficient cell lines. Similar results were observed when a mitogen-stimulated peripheral blood lymphocyte culture from an xeroderma pigmentosum A patient was assayed concurrently with mitogen-stimulated peripheral blood lymphocytes obtained from healthy individuals. Adaptation of this DNA repair assay as a field test in a pilot-tested select group of basal cell carcinoma patients and cancer-free controls led to the preliminary identification of a specific subset at risk for this disease as a consequence of significant reduction to the repair of photochemically (UV)-damaged plasmid DNA.

DNA repair related to multiple skin cancers and drug use.

Defective repair of sunlight-induced DNA photodamage, coupled with an unusually high occurrence of multiple primary basal cell carcinomas (BCCs), is the major characteristic of xeroderma pigmentosum. Our recent work has indicated that this etiological paradigm may apply to skin cancer patients without an apparent hereditary disease. The present study reports on an investigation of whether medications such as photosensitizing drugs (antibiotics, corticosteroids, and aspirin) modulate skin cancer risk through alterations in DNA repair capacity (DRC). Using a new DNA repair (host cell reactivation) assay with peripheral T-lymphocytes, we tested DRCs of 88 Caucasian BCC patients and 135 cancer-free controls. Subjects were between 20 and 60 years of age and free of known hereditary skin diseases. The age-adjusted means of DRC were calculated to compare repair levels associated with the use of specific drugs and hormones. Multiple linear regression models were used to correlate DRC with the number of skin cancers. The estimated odds ratio was used to describe the risk of BCCs. The distribution of DRCs of subjects was approximately normal, with a 5-fold variation between individuals. DRCs below the upper 30th percentile of controls were associated with an estimated 2.3-fold (95% confidence interval, 1.17-4.54-fold) increased risk for the occurrence of BCCs. The lower the DRC was, the greater the number of skin tumors in individuals (P < 0.05), after adjustment for age. Although supplemental vitamin use was associated with reduced risk of skin cancer, it was not associated with differences in subjects' DRCs. However, individuals who reported taking either tetracycline or estrogen, two photosensitizing drugs, had higher DRCs, compared with those who had not used these drugs. Low DRC or a family history of skin cancer increased the probability that patients who were overexposed to sunlight would have multiple BCCs. DNA repair levels may be influenced by the use of selected photosensitizing drugs and estrogen.

Phase I trial of intravenous cyclosporine to induce graft-versus-host disease in women undergoing autologous bone marrow transplantation for breast cancer.

PURPOSE: We investigated if graft-versus-host disease (GVHD), which is associated with an antitumor effect, could be induced in women with advanced breast cancer by treatment with cyclosporine (CSA) following reinfusion of purged autologous marrow after treatment with high-dose chemotherapy and defined the toxicities of this approach. PATIENTS AND METHODS: Fifty-one women with advanced breast cancer responding to therapy were treated with escalating doses of CSA (1.0, 2.5, or 3.75 mg/kg/d) for 28 days following high-dose chemotherapy and autologous bone marrow transplantation and monitored for induction of GVHD and toxicity of therapy. RESULTS: GVHD was induced in a dose-dependent fashion in 14%, 68%, and 92% of patients at each dose level, respectively, a median of 15 days following autologous marrow reinfusion. GVHD was clinically mild and limited to skin. Toxicity was acceptable, with two deaths within 50 days of marrow reinfusion. Statistically significant increases in maximum creatinine and bilirubin levels were seen at all dose levels when compared with similarly treated historic controls who did not receive CSA. Time to last platelet transfusion was significantly delayed in patients treated at the highest dose. CONCLUSION: GVHD can be safely induced by treatment with CSA in women with advanced breast cancer who are receiving high-dose alkylating agents and autologous bone marrow transplantation. The toxicity of this approach is acceptable. Evidence of antitumor efficacy awaits further investigation.

Phase I trial of interferon gamma to potentiate cyclosporine-induced graft-versus-host disease in women undergoing autologous bone marrow transplantation for breast cancer.

PURPOSE: We investigated if interferon gamma (IFN-gamma) could augment cyclosporine (CSA)-induced graft-versus-host disease (GVHD) following autologous bone marrow transplant in women with metastatic breast cancer and defined the toxicities of this therapy. PATIENTS AND METHODS: Thirty-six women with advanced breast cancer were treated with CSA 2.5 mg/kg daily for 28 days and IFN-gamma 0.025 mg/m2 subcutaneously (SC) every other day, days 7 to 28 following autologous bone marrow transplantation and monitored for induction and severity of GVHD and toxicity of therapy. RESULTS: GVHD was induced in 56% of patients. The severity of GVHD was greater than in a historic control population treated with CSA alone. Stage III rash was seen in 36% of patients, compared with 3% in the historic control population. Fourteen of 36 patients required therapy with topical corticosteroids and two of 36 required systemic treatment. Only three of 31 historic controls needed topical corticosteroids and no patient was treated systemically. There was no severe visceral GVHD. Hematopoietic recovery was not delayed. There were three toxic deaths. CONCLUSION: CSA-induced GVHD can be safely augmented by IFN-gamma in women treated with high-dose alkylating agents and autologous bone marrow transplantation. There is little evidence of increased toxicity. Evidence of antitumor efficacy awaits further investigation.

Human cutaneous graft-versus-host disease.

The natural history of human cutaneous graft-versus-host disease (GVHD) has been described as a consequence of allogeneic bone-marrow transplants, but syngeneic and even autologous marrow transplants are now being recognized as being associated with similar, albeit less severe, changes. The histopathologic changes of both acute and chronic GVHD have been reported and show similarities to other idiopathic cutaneous disorders. The T-lymphocyte, specifically an OKT8+ cell, seems to play a major role in the pathogenesis of cutaneous GVHD. A recently described in vitro model of human cutaneous GVHD using skin explants co-cultured with lymphocytes holds some promise as a technique to further explore lymphocyte-skin interactions.

DNA repair capacity for ultraviolet light-induced damage is reduced in peripheral lymphocytes from patients with basal cell carcinoma.

Sunlight exposure and certain host factors such as red hair and fair skin are established risk factors for non-melanoma skin cancers. Because deficient DNA repair capacity has contributed to the development of skin cancers in a rare genetic disease, xeroderma pigmentosum, we explored this deficiency as an etiologic factor in a recent population study. We used a new DNA repair assay, the host-cell reactivation, in a clinic-based case-control study to test the hypothesis that reduced DNA repair is the underlying molecular mechanism for the development of sunlight-induced basal cell carcinoma. The peripheral lymphocytes from 88 patients with primary BCC and 135 cancer-free controls were tested for their capacity to repair ultraviolet light-induced DNA damage in a reporter gene, chloramphenicol acetyl transferase. All subjects were between the ages of 20 and 60 years and were frequency matched by age (+/- 5) and sex. Among those who reported frequent sunbathing, poor tanning ability, a history of multiple sunburns, exposure to chemicals, or multiple medical irradiations, the BCC patients had significantly lower DNA repair capacity than controls (p < 0.05). DNA repair capacity was also found substantially lower in the basal cell carcinoma patients who had red hair and light skin (type I). Compared to controls, basal cell carcinoma cases with selected risk factors had a relative decrease in DNA repair capacity of 10-28%. These findings provided evidence that reduced DNA repair capacity is one of the underlying molecular mechanisms for sunlight-induced skin carcinogenesis in the general population.

Clinical, laboratory, and histopathologic indicators of the development of progressive acute graft-versus-host disease.

Graft-versus-host disease (GvHD) is the major cause of morbidity and mortality following bone marrow transplantation (BMT). The goal of this study of 69 cyclosporin-treated, allogeneic BMT patients was to identify early clinical, laboratory, or histopathologic indicators of the development of progressive, fatal GvHD. Peak values within 100 d of allogeneic BMT for total bilirubin, stool volume in a day, clinical stage of cutaneous GvHD (based on extent of rash), and overall clinical stage of GvHD (based on a combination of graft-versus-host reactions in the skin, liver, and gastrointestinal tract) were most useful (p less than 0.05, by logistic regression) in identifying those patients with clinically progressive and fatal GvHD. Peak values for each of these parameters were reached an average of 40 d or less after BMT. Each unit increase in peak clinical stage of rash (e.g., stage 2 versus stage 3) was associated with an odds ratio incremental risk of 5.8 for clinical progression of GvHD, and each tenfold increase in peak total bilirubin (e.g., 2 mg/dl versus 20 mg/dl) or stool output in a day (e.g., 100 cm3/d versus 1000 cm3/d) was associated with an incremental risk of 8.4 and 10.6, respectively, for a fatal outcome from GvHD. Number of exocytosed lymphocytes and dyskeratotic epidermal keratinocytes (DEK) per linear millimeter of epidermis, the presence of follicular involvement, and the degree of dermal perivascular lymphocytic infiltration in 121 skin biopsy specimens were not associated with the development of progressive or fatal GvHD. Pretransplant total body irradiation was associated (p = 0.03, by Mann-Whitney U testing) with an increased number of DEK in skin biopsy specimens taken less than 20 d after BMT. This study demonstrates that monitoring of total bilirubin, stool output, extent of rash, and overall clinical stage of GvHD is most useful during the first 40 d after BMT in formulating the prognosis of early acute GvHD in allogeneic BMT patients receiving cyclosporin.

Cutaneous graft-versus-host reaction lacks evidence of cutaneous cytomegalovirus by the immunoperoxidase technique.

Sixty skin biopsy specimens from 21 bone-marrow transplant patients were evaluated for the presence of cytomegalovirus (CMV) using two monoclonal antibodies to early and late antigens. Each patient had at least one biopsy showing an acute graft-versus-host reaction (GVHR), grade 2, and one positive culture for CMV from blood, bone marrow or urine. In no case could CMV antigens be identified in biopsies showing an acute or chronic cutaneous GVHR or in any other of the skin biopsies obtained from these patients. While CMV may play a role in immunologic events culminating in graft-versus-host disease (GVHD), this immunoperoxidase study did not reveal evidence of viral antigens in tissue displaying features of cutaneous GVHR.

The use of monoclonal antibody to keratin in human epidermal disease: alterations in immunohistochemical staining pattern.

A monoclonal antikeratin antibody, designated AEl, was used to stain frozen sections of normal and abnormal human skin by the immunofluorescence and peroxidase-antiperoxidase techniques. In normal human epidermis and ichthyosis vulgaris, a nonproliferative epidermal disease, this antibody selectively stained epidermal basal cells. Very different staining patterns were observed in various other epidermal diseases. A suprabasal staining pattern was observed in psoriasis (16 cases), verruca (9), seborrheic keratosis (5), actinic keratosis (2), as well as the epidermis adjacent to certain epidermal neoplasms (4). Basal cell carcinoma (7) showed weak, homogeneous staining. In contrast, a disorganized pattern consisting of cells with various staining intensities was observed in Bowen's disease (2) and squamous cell carcinoma (4). Although the biochemical basis for these altered staining patterns remains to be elucidated, these results provide further evidence that epidermal keratin expression can be affected by various disease states. Moreover, our data suggest that a common alteration in keratin expression, as defined by the suprabasal AEl staining pattern, exists in psoriasis and a number of other benign hyperproliferative epidermal diseases.

Epithelial class II antigen expression in cutaneous graft-versus-host disease.

Induced class II histocompatibility antigens have been observed in the target tissues of rodents and humans with acute graft-versus-host disease (GVHD). Possibly this expression triggers the target tissue phase, through antigen presentation, lymphocyte recruitment, or additional antigenic stimulus. We have tested whether the induced expression is required for cutaneous GVHD in human marrow recipients. Ninety-two skin biopsies from 37 allogeneic marrow recipients at the Johns Hopkins Bone Marrow Transplant Unit were stained for HLA-DR, OKT6 (Langerhans cells), and for surface markers of lymphocyte and monocytes. Of 22 biopsies taken at the onset of GVHD, 12 did not have detectable HLA-DR antigen, and 10 had patchy-to-diffuse expression. The biopsies with HLA-DR- GVHD consisted primarily of epithelial infiltrates of cytotoxic/suppressor cells (CD8+), while those with HLA-DR+ GVHD had a mixed infiltrate with more helper/inducer/class-II-reactive cells (CD4+) in the epidermis and dermis and more monocytes in the dermis. Eight of 9 patients with HLA-DR- GVHD had follow-up biopsies that later expressed epithelial DR antigen, but the epidermal and dermal infiltrates showed no significant changes. Most of those receiving cyclosporine (CsA) prophylaxis (7/9) developed HLA-DR- GVHD, while those receiving cyclophosphamide were split between the two groups (8 of 13 were HLA-DR+). HLA-DR antigen expression was evident in some biopsies with no GVHD or minimal GVHD but did not appear to predict the development of GVHD or the type of GVHD. HLA-DR antigen expression was not evident in 2 of 3 initial biopsies of lichenoid-type chronic GVHD. Class II antigen induction is clearly not necessary for the target phase in most patients of this study.

Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists.

The reliability of a diagnostic test depends on the reproducibility of the result. Many clinical diagnostic tests can be quantified with established ranges and standard deviations. Other tests are more subjective, such as those that depend on analysis of a visual image with an increased possibility of variance in the result. To study this variance, the authors analyzed the performance of expert pathologists in the interpretation of cutaneous melanocytic tumors. A panel of expert pathologists was convened to review anatomic pathology specimens from melanocytic tumors. Each pathologist submitted five specimens, from which 37 were selected for review. Only one slide was used for each case. All specimens were interpreted by each pathologist without consultation with each other. In addition to standard diagnostic terms, each specimen was designated as benign, malignant, or indeterminate. Statistical analysis was used to determine the degree of concordance. The combined kappa statistic for the eight observers and three possible outcomes (benign, malignant, or indeterminate) was 0.50. A kappa statistic of this magnitude, is defined as being moderate. In 62% of the specimens, there was unanimous agreement or only one discordant designation. Thirty-eight percent had two or more discordant interpretations. No single pathologist had a disproportionate number of discordant designations. This study mimics the consultation practice of anatomic pathology and shows the variability and discordance in diagnostic language and designation of biological behavior. The results suggest the criteria for the diagnosis of melanomas and melanocytic nevi need to be refined and more consistently applied.

Vitamin supplementation and reduced risk of basal cell carcinoma.

A clinic-based case-control study was conducted to determine the association between vitamin supplement use and risk of basal cell carcinoma (BCC) of the skin. The subjects were 131 patients with histopathologically confirmed primary BCC and 200 cancer-free controls with non-premalignant skin disorders. Use of any vitamins (mainly multivitamins and vitamins A, C, and E) was associated with reduced risk of BCC. After controlling for age, sex, cigarette smoking, number of lifetime severe sunburns, and skin actinic elastosis, regular vitamin supplementation was associated with a significantly reduced risk of BCC (odds ratio (OR) = 0.3; 95% confidence interval (CI) = 0.2-0.06). The ORs decreased as the regularity (p < 0.001) and daily doses of supplement used increased, especially for vitamins A (p < 0.005) and E (p < 0.005). Vitamin supplementation was not associated with alterations in cellular DNA repair. These results, however, cannot be considered conclusive because of the relatively low participation rates (131/830 for cases and 200/1406 for controls) due to the requirement of blood donation and more rigorous studies are needed to clarify the effect of supplemental vitamins, particularly of vitamins A and E, on the risk of BCC of the skin.

Growth retardation and depigmentation of hair after high-dose busulfan and congenic hematopoietic cell transplantation in mice.

Busulfan, a myeloablative but non-immunosuppressive alkylating agent, is used extensively in clinical bone marrow transplantation (BMT), but the effects of high-dose administration have not been previously evaluated in preclinical BMT settings with young murine recipients. We compared the survival and growth of C57BL/6 mice given graded single doses of busulfan (10-100 mg/kg) or total body irradiation (TBI; 900 cGy) at age 9 days and hematopoietic cell transplantation (HCT; transplantation of congenic bone marrow and spleen cells) 24 h later. The 30-day survival was 87-100% in mice transplanted after 10-40 mg/kg busulfan and 79% after TBI, but fell to 54% and 33%, respectively, after 80 mg/kg and 100 mg/kg busulfan, suggesting that this latter dosage range represents the LD50 for single-dose busulfan in young C57BL/6 mice given stem cell rescue. The weights of 10-week-old mice given HCT after lower doses of busulfan ranged from 87% of control at 10 mg/kg to 64-69% of control in mice conditioned with 35-65 mg/kg busulfan or TBI. Impairment of weight gain was most striking (approximately 50% of control) in mice transplanted after 80-100 mg/kg busulfan. Despite retardation of somatic growth, the brain weights of busulfan-conditioned mice remained at least 90% of control, and there were no obvious neuropathological alterations in the brains of these animals. All mice treated with at least 20 mg/kg busulfan or TBI lost hair by 3-4 weeks after transplant.(ABSTRACT TRUNCATED AT 250 WORDS)

The eye in bone marrow transplantation. III. Conjunctival graft-vs-host disease.

Of a series of 263 patients undergoing allogeneic bone marrow transplantation (BMT), 24 patients developed conjunctival involvement by graft-vs-host disease (GVHD). In each case, a distinct-appearing conjunctivitis developed that representing GVHD of the conjunctiva. In 19 cases (79%), conjunctival GVHD presented with pseudomembrane formation due to loss of the conjunctival epithelium; in 4 of these cases, the corneal epithelium was lost as well. Nineteen patients developed this feature in association with acute GVHD, and mortality among these patients was 89.5%. Kaplan-Meier analysis of survival demonstrated a decreased survival of patients with conjunctival involvement compared with all marrow transplant recipients and compared with all patients with GVHD. However, survival was similar to that seen in patients with severe systemic GVHD (overall stages II through IV). Five patients developed conjunctival GVHD in association with chronic GVHD, and all had severe chronic GVHD. four of these five with chronic GVHD subsequently died. Conjunctival involvement by GVHD represents a distinct clinical finding and is a marker for severe systemic involvement by GVHD. A clinical staging system for ocular involvement was formulated.

Cyclosporine-induced graft-versus-host disease after autologous bone marrow transplantation for acute myeloid leukemia.

Rodents given cyclosporine (CSP) for several weeks after autologous or syngeneic bone marrow transplantation develop a syndrome that mimics allogeneic graft-versus-host disease (GVHD). Autologous GVHD has also been reported after administration of CSP in patients who have received autologous bone marrow transplantation (ABMT) with untreated marrow for lymphoma or acute myeloid leukemia (AML). Our study was designed to determine whether CSP administration is associated with appearance of autologous GVHD in patients with AML receiving ABMT with 4-hydroperoxycyclophosphamide (4HC)-purged marrow and whether there was a dose-dependent effect of CSP on development of the syndrome. Thirty-three patients with AML (18 in first remission [CR1], 10 in CR2, and 5 in CR3) received intravenous CSP, beginning on the day of ABMT, after a preparative regimen of busulfan and cyclophosphamide and ABMT with 4HC-treated marrow. Skin biopsies were obtained weekly after ABMT or on appearance of rash and were graded for GVH changes. In the first phase of this study, groups of patients received CSP dosages of either 1 mg/kg/day (7 patients), 2.5 mg/kg/day (8 patients), or 3.75 mg/kg/day (6 patients) for 28 days. Sixteen of the 21 patients (76%) developed cutaneous histopathologic grade 2 GVHD at a median of 34 days (range, 14-49) after ABMT, and cutaneous manifestation were present at time of positive biopsy in 11 of the 16 patients. There was no apparent difference in frequency, time to onset, or duration of GVHD among the three CSP dosage groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Cutaneous ciliated cysts.

We studied 11 patients with a cutaneous cyst lined by a simple columnar ciliated epithelium. All of the patients were women in the second or third decade of life. Each had only a single lesion, located on the lower extremity. Clinical examination showed a cyst without specific identifying characteristics. The cyst is considered benign, because of the high degree of differentiation and lack of cellular atypia. The origin of the cyst is unknown. We favor the theory of sequestration and migration over that of transplantation or metaplasia.