Increased frequency of autoaggression syndrome associated with autologous stem cell transplantation in breast cancer patients.

In our BMT Unit, we have observed a high frequency of skin rash associated with fever and other clinical findings during engraftment of autologous BM and/or PBSC. Thirty patients with breast cancer and 12 patients with Hodgkin's or non-Hodgkin's lymphoma, treated with the same regimen, were analyzed retrospectively or prospectively to characterize the clinical syndrome, its frequency, and its clinical course, as well as to define the factors affecting its incidence. In patients developing skin rash, the median and range for time to onset of skin rash and for time to increase in WBC after reinfusion of stem cells were identical (8 days, range 5-13) and did not differ significantly (P = 0.533). Twenty-three patients (55%) had skin rash, 18 patients had fever. Other, less frequent manifestations include platelet transfusion refractoriness (PTR), diarrhea, diffuse alveolar hemorrhage, and autoimmune thrombocytopenia or hemolytic anemia. A higher proportion of breast cancer patients developed the syndrome in comparison to lymphoma patients (67% vs 25%, P = 0.051). Acute GVHD grade I-II was established histologically in six patients with the syndrome. Comparison of the incidence of the syndrome by different variables using Fisher's exact test revealed significance for disease category (P = 0.02) and number of previous treatment regimens (P = 0.002) as predictive factors for developing the autoaggression syndrome. In other words, patients with breast cancer and those with only one previous treatment regimen were more likely to develop the syndrome. This study suggests that an autoaggression GVHD-like syndrome accompanies the early phase of autologous engraftment and that a higher frequency of the syndrome might be seen in breast cancer patients undergoing high-dose chemotherapy and autologous stem cell transplantation.

Androgen responsive genes as they affect hair growth.

Finasteride has been shown to be an effective treatment for men with androgenetic alopecia (AGA) as it restores hair growth to miniaturized hair follicles on the top of the scalp [1]. Caspases are regulators of programmed cell death, and very likely some specific caspases may function as mediators of the hair growth cycle. It is unclear whether finasteride influences the regulation of apoptosis via caspases in the hair follicle. Very little information is available regarding the role of caspases present in human hair follicles in normal scalp and in androgenetic alopecia. In this study we have analyzed the family of caspases, 1-10 along with usurpin, and XIAP, in men with normal scalp and in men with androgenetic alopecia before and after 6 months treatment with 1 mg oral finasteride treatment. Caspases 1, 3, 8 and 9 were detected predominantly within the isthmic and infundibular hair follicle area for both normal and AGA patients, however the expression of all factors, especially caspase 3 was greater in the AGA group than in the normal scalp group. AGA men had the same caspase factors but with greater expression. In the same AGA men treated with finasteride for 6 months, the expression of these factors was similar to levels in the normal group. Results from our study indicate caspase 3 to be of primary importance in normal hair homeostasis and that DHT may be signaling greater expression of caspases, inducing apoptosis in androgenetic alopecia. In conclusion, DHT may selectively regulate the caspase genes which play an important role in signaling programmed cell death, affecting the hair growth cycle.

Crossed ectopia of ovotestis in a case of true hermaphroditism.

True hermaphroditism is a rare form of intersex disorder. The authors report a case of true hermaphroditism with crossed ectopia of an ovotestis from the left to the right scrotum. The karyotype of the patient was 46,XX, without mosaicism. The majority of the ovotestis was comprised of testicular tissue. In other cases of human true hermaphroditism, descent of a pure ovary has not been noted to occur, despite the presence of the contralateral testis. Additionally, in congenital adrenal hyperplasia occurring in genotypic female subjects, pure ovaries do not descend into the scrotum despite the high level of androgens. Taken together, we believe that the demonstrated descent of mostly testicular ovotestes supports the idea that the testis produces a substance other than androgen that is important in guiding its descent.

Automated rescreening in cervical cytology. Mathematical models for evaluating overall process sensitivity, specificity and cost.

OBJECTIVE: To develop mathematical models to assist decision makers with the difficult task of evaluating the use of automated rescreening in the process of screening cervical smears. STUDY DESIGN: Using assumptions about incidence, per smear screening costs, and the sensitivity and specificity of cytotechnologists, pathologists and the rescreening device, basic probability models were developed to describe the overall sensitivity, specificity and cost of the screening process. RESULTS: The optimal screening policy is highly dependent on assumptions, and an automated system can significantly affect the overall system cost and accuracy. CONCLUSION: Mathematical planning models are valuable tools to assist decision makers in the design of a screening process for cervical smears.

Statistical analysis of data in cervical cytology from the viewpoint of total quality management.

As a consequence of widespread dissatisfaction with the high incidence of false negatives in cytologic smear screening, the Clinical Laboratory Improvement Amendments of 1988 were enacted by Congress with specific requirements for quality assurance in the screening of cytologic smears for cervical cancer. This paper examines the process of cervical cytologic screening from a total quality management perspective and suggests the use of several statistical techniques from industrial total quality management for describing and monitoring the process of cytologic smear screening. Several examples are included, and a general approach to implementing these techniques is suggested.

Rescreening policies in cervical cytology and their effect on detecting the truly positive patient.

In the use of a specific screening policy that relies on the expertise of cytotechnologists and pathologists to examine cytologic smears for the detection of cervical cancer, it is important to know the probability of correctly identifying a positive patient and, for each 1,000 patients, to know the probability distribution, the expected value and the standard deviation of the number of correct identifications. A probability model for the standard 10% rescreening rule mandated by the Clinical Laboratory Improvement Act of 1988 and Medicare was developed and used to evaluate higher screening rates. In addition, the model is applied to an alternative screening policy to study multiple inspections by a specific number of cytotechnologists prior to rescreening by a pathologist. For each policy the probability distribution, expected value and standard deviation of the number of correct identifications per 1,000 positive patients are given.

An economic model for comparing alternative policies for cervical cytologic smear screening.

In this paper a mathematical model is developed to determine the probability that a truly negative cervical cytologic smear will be correctly identified by a system of screening policies that uses one or more cytotechnologists to independently and sequentially prescreen such smears for the detection of cervical cancer. This is an extension of previous work that modeled the probability of detecting a truly positive smear under the same set of policies. In this system any positive reading by a cytotechnologist causes a slide to be rescreened by a pathologist, and if all cytotechnologists declare a slide to be negative, the slide is placed in a pool for random selection of slides to be rescreened by the pathologist. The policy of single screening by a cytotechnologist, with subsequent 10% rescreening of the negative slides, as suggested by the Clinical Laboratory Improvement Amendments of 1988, is thus embedded in the policies that are modeled. In addition, a cost model is developed that takes into account the cost of screening a slide by a cytotechnologist, of rescreening a slide by a pathologist, of a false-positive reading and of a false-negative reading. This cost model can be used to determine which policy is optimal for the parameters that pertain to a specific situation. Examples are presented to illustrate the use of the cost model. The results of a computer simulation model are also presented to validate the mathematical results and to display the variability of total cost.

Pathology of the vulva and vagina.

Extensive clinical, epidemiologic and pathologic research published in the past year has enhanced our understanding of the pathogenesis and natural history of human papillomavirus induced female genital tract lesions, and refined diagnostic and therapeutic modalities in management of these patients. Current experience with vulvar intraepithelial neoplasia as well as diagnosis and treatment of squamous cell carcinoma of the vagina and vulva are discussed. Advanced imaging techniques and immunohistochemical studies are employed in diagnosis and classification of less common neoplasms. New antibiotics and potent topical steroids are available for treatment of inflammatory vulvovaginitis, particularly in cases of recurrent candidiasis and lichen sclerosus. Persistent or resistant vulvovaginitis may benefit from an interdisciplinary approach to diagnosis and treatment.

Using SPC (statistical process control) to analyze measurements in a healthcare organization.

This article presents a tutorial on statistical process control (SPC) for measurement data and the use of trial control charts. Examples from healthcare applications are used to illustrate one process in statistical control and two other processes not in statistical control.

Frequency of pre-existing actinic keratosis in cutaneous squamous cell carcinoma.

BACKGROUND: Controversy over the rate of malignant transformation of actinic keratosis (AK) into cutaneous squamous cell carcinoma (SCC) has generated considerable debate regarding the importance of treating all such precancers to preclude their transofrmation. Current changes in US healthcare policy will deny many individuals access to certain simple and effective treatment modalities for precancerous lesions. OBJECTIVE: Our purpose was to determine whether there is a significant association between the presence of cutaneous SCC and pre-existing AK. METHODS: One hundred and sixty five consecutive cases of cutaneous SCC, retrieved from the files of a university-affiliated dermatopathology laboratory serving north-central Florida, were selected for review by a single dermatopathologist (D.M.). Hematoxylin and eosin stained skin tissue slides were examined under light microscopy for the presence of AK in close proximity to, or giving rise to, cutaneous SCC. RESULTS: Of the 165 cutaneous SCC cases reviewed, 82.4% (136 out of 165) were found to have concomitant AK giving rise to and/or in close proximity to SCC. Of the 136 AK-positive SCC cases, 26.7% (44) were identified as superficial SCC arising within an AK (AKSSCC) and 55.7% (92) had AK in close proximity to SCC (AK + SCC). Close proximity is defined to include AK changes located directly adjacent to (on the shoulder of) SCC, to a maximum distance of 8 mm away. CONCLUSIONS: The 82.4% prevalence of concomitant AK and cutaneous SCC in our biopsy population suggests a strong correlation between these two lesions. The fact that 26.7% of these lesions had SCC arising from AK highlights the importance of early recognition and effective treatment for AK.

Ischemic colitis and acquired resistance to activated protein C in a woman using oral contraceptives.

We present the case history of a 22-yr-old woman diagnosed with ischemic colitis associated with the use of oral contraceptives (OC). At the time of her presenting symptoms activated protein C (APC) resistance, a risk factor for thrombosis, was demonstrated. There was no laboratory evidence of inherited thrombophilia; that is, antithrombin III, protein C and protein S levels were normal and the factor V Leiden mutation was not present. The OC were discontinued and the patient's symptoms improved. Subsequent evaluation revealed that the activated protein C resistance had resolved. This case illustrates APC resistance as a potential link between OC use and its known association with ischemic colitis.