Implementation of an electronic data monitoring system decreases the rate of hyperoxic episodes in premature neonates.

OBJECTIVE: To determine whether an electronic data surveillance system, or Data Sniffer (DS), could reduce the rate of hyperoxic episodes (HEs) among premature neonates being managed by a standardized respiratory treatment protocol (RTP). STUDY DESIGN: A total of 86 infants born at <29 weeks of gestation were included in the study. The rates of HEs were compared among four epochs (E) as follows: E1: no RTP, no DS; E2:with RTP, no DS; E3: with RTP, with DS; E4: with RTP, no DS. RESULT: After implementing the RTP in E2, the rate of HEs was 44% lower than that of E1. Activating the DS in E3 further reduced HEs by 26%, whereas its deactivation in E4 resulted in a rebound in HEs to baseline rates; P<0.0001 for each comparison. CONCLUSION: The implementation of an electronic data monitoring system was associated with less frequent episodes of hyperoxia among premature neonates.

Concentrations of nonesterified fatty acids and glucose in blood of periparturient dairy cows are indicative of pregnancy success at first insemination.

Greater blood concentrations of nonesterified fatty acids (NEFA) and lesser blood concentrations of glucose are indicative of the normal process of nutrient partitioning that occurs in early postpartum dairy cows. The objective was to determine the relationship between blood NEFA and glucose concentrations and subsequent conception at first insemination in postpartum dairy cows. Holstein (n=148) and Guernsey (n=8) dairy cows were blood sampled at approximately d 10, 7, and 3 prepartum, on the day of calving and 3, 7, 14, and 21 d postpartum for measurement of NEFA and glucose concentrations. Serum and plasma were harvested and used for measurement of NEFA and glucose concentrations, respectively. Cows were given a presynchronization treatment (2 injections of PGF(2α) 14 d apart) with the second PGF(2α) injection occurring 14 d before the initiation of the timed AI (TAI) protocol. Blood for determination of progesterone concentrations was collected at each presynchronization injection and at the initiation of the TAI protocol that was used for first insemination (74±7 d postpartum). Cows were considered noncycling if serum progesterone concentrations at the 2 presynchronization PGF(2α) injections (d 37 and 51±7 postpartum) and at the initiation of the TAI protocol (d 65±7 postpartum) were ≤1 ng/mL, and there was no indication of ovulation or presence of a corpus luteum by ultrasound examination at the initiation of the TAI protocol. Pregnancy was determined at 33 d and again at 61 d after first insemination by using ultrasound. Across all days, serum NEFA and plasma glucose concentrations were not different between cows that ovulated before the initiation of the TAI program (cycling) compared with those that did not ovulate (noncycling). Serum NEFA concentrations, however, were less and plasma glucose concentrations were greater during the early postpartum period for cows that subsequently became pregnant at first insemination compared with those that failed to become pregnant. Logistic regressions were used to predict the probability of pregnancy based on NEFA and glucose concentrations from individual days. The prediction with the greatest likelihood ratio was for d 3 postpartum NEFA and glucose concentrations. Nutritional status during the early postpartum period (within 1 wk after calving), as indicated by blood NEFA and glucose concentrations, may affect subsequent fertility by a mechanism that is independent from interval to first ovulation.

Double-blind trial of a polyvalent, shed-antigen, melanoma vaccine.

A polyvalent melanoma vaccine prepared from shed antigens stimulates humoral and cellular immune responses and improves survival compared with historical controls. We conducted a double-blind, prospectively randomized, placebo-controlled trial to assess whether this vaccine could slow the progression of resected melanoma. Thirty-eight patients with resected melanoma metastatic to regional nodes (American Joint Committee on Cancer stage III) who had a particularly poor prognosis on the basis of the nodes being clinically positive or two or more histologically positive nodes were randomly assigned in a 2:1 ratio to treatment with 40 microg of melanoma or placebo (human albumin) vaccine, both of which were bound to alum as an adjuvant. Immunizations were given intradermally into the extremities every 3 weeks x 4, monthly x 3, every 3 months x 2, and then every 6 months for 5 years or until disease progression. Twenty-four patients were treated with the melanoma, and 14 patients were treated with the placebo vaccine. The groups were evenly balanced with respect to prognostic factors. Median length of observation was 2.5 years. There was no local or systemic toxicity. By Kaplan-Meier analysis, median time to disease progression was two and a half times longer in patients treated with melanoma vaccine compared with that in patients treated with placebo vaccine, i.e., 1.6 years (95% confidence interval, 1.0-3.0 years) compared with 0.6 year [95% confidence interval, 0.3-1.9 year(s)]. By Cox proportional hazards analysis, this difference was significant at P = 0.03. Overall survival was 40% longer in the melanoma vaccine-treated group (median overall survival of 3.8 years versus 2.7 years), but this difference was not statistically significant. In a double-blind and placebo-controlled trial, these results suggest that immunization with a melanoma vaccine may be able to slow the progression of melanoma. Although statistically significant, these results must be interpreted with caution because they are based on a small number of patients.

Kinetic and mechanistic studies of prolyl oligopeptidase from the hyperthermophile Pyrococcus furiosus.

Prolyl oligopeptidase (POP) is widely distributed in mammals, where it is implicated in neuropeptide processing. It is also present in some bacteria and archaea. Because POP is found in mesophilic and hyperthermophilic organisms, and is distributed among all three phylogenetic domains, studies of its function and structure could lead to new insights about the evolution of enzyme mechanisms and thermostability. Kinetic studies were conducted on the POP of the hyperthermophilic archaeon Pyrococcus furiosus (Pfu) 85 degrees C in both H(2)O and D(2)O. Pfu POP displayed many similarities to mammalian POPs, however the solvent isotope effect (k(0)/k(1)) was 2.2 at both high and low pH, indicating that general base/acid catalysis is the rate-limiting step. The pH-rate profiles indicated a three-deprotonation process with pK(a) values of 4.3, 7.2, and 9.1. The temperature dependence of these values revealed a heat of ionization of 4.7 kJ/mol for pK(es1) and 22 kJ/mol for pK(es2), suggesting the catalytic involvement of a carboxyl group and an imidazole group, respectively. Temperature dependence of the catalytic rate was assessed at pH 6.0 and 7.6. Entropy values of -119 and -143 Jmol(-1)K(-1) were calculated at the respective pH values, with a corresponding difference in enthalpy of 8.5 kJ/mol. These values suggest that two or three hydrogen bonds are broken during the transition state of the acidic enzyme form, whereas only one or two are broken during the transition state of the basic enzyme form. A model has been constructed for Pfu POP based on the crystal structure of porcine POP and the sequence alignment. The similarities demonstrated for POPs from these two organisms reflect the most highly conserved characteristics of this class of serine protease, whereas the differences between these enzymes highlights the large evolutionary distance between them. Such fundamental information is crucial to our understanding of the function of proteins at high temperature.

Decrease in circulating tumor cells as an early marker of therapy effectiveness.

As melanoma cells are present in the circulation of many patients with this cancer, decreases in their number could provide an early indication of therapy effectiveness. To evaluate this possibility, we examined the effect of treatment with a melanoma vaccine on the number of melanoma cells present in the circulation. PCR was used to detect melanoma cells that expressed the melanoma-associated antigens MART-1, MAGE-3, tyrosinase and/or gp100 in 91 patients with melanoma. Melanoma cells that expressed one or more of these markers were present more often in advanced disease, i.e. in 80% of patients with advanced stage IV compared to in less than one-third of patients with less advanced disease. We then measured circulating melanoma cells in a subset of 43 of these patients who were treated with a polyvalent, shed antigen, melanoma vaccine. The vaccine contains multiple melanoma-associated antigens including MART-1, MAGE-3, tyrosinase and gp100. Immunizations were given intradermally q2-3 weeks x4 and then monthly x3. Prior to vaccine treatment, circulating melanoma cells were detected in 14 (32%) patients. Following 4 and 7 months of vaccine treatment, melanoma cells that expressed any of these markers were present in only nine (21%) and three (7%) of patients, respectively. Thus, vaccine therapy was associated with clearance of melanoma cells from the circulation in 78% of initially positive patients. As the number of these cells declined steadily with increasing length of therapy, it is unlikely that this was due to a random change in their number. Rather it suggests that the decline was a result of the therapy. These observations suggest that the presence of melanoma cells in the circulation is related to the extent of the melanoma, and that their disappearance may provide an early marker of the efficacy of therapy. However, the practical utility of assaying circulating tumor cells as a guide to the effectiveness of therapy or of prognosis will need to be confirmed by correlations with clinical outcome.

Congenital spitz nevus.

BACKGROUND: Congenital Spitz nevus has been reported previously in the literature, but the histopathologic features have not been examined in detail. OBJECTIVE: To histologically examine and report on congenital Spitz nevus. METHOD: We examined 10 clinically submitted congenital melanocytic nevi that were histopathologically identified as congenital Spitz nevi and compared them to the characteristics seen in acquired Spitz nevus and superficial congenital melanocytic nevus. RESULTS: Of the 10 congenital Spitz nevi, 9 were compound and 1 was dermal. Two showed features of combined Spitz nevus (Spitz and blue). Six cases showed all 16 listed characteristics of acquired Spitz nevus, with two cases having 15 and two cases having 14 characteristics. Of the superficial congenital melanocytic nevus characteristics, all except three cases had all 12 attributes. The one dermal lesion had all the characteristics of the acquired Spitz nevus and all but one of the characteristics of the superficial congenital melanocytic nevus in regards to intradermal findings. CONCLUSIONS: Congenital Spitz nevi are true congenital lesions, with histopathologic features of both acquired Spitz nevus and superficial congenital melanocytic nevus.

Aspiration biopsy and the clinical management of patients with malignant melanoma and palpable regional lymph nodes.

BACKGROUND: The presence of lymph node metastases in patients with malignant melanoma implies a significant decrease in survival. The authors investigated the efficacy of fine-needle aspiration biopsy (FNAB) in the diagnosis of metastatic malignant melanoma in 115 patients with melanoma and clinically suspicious regional lymph nodes. METHODS: One hundred thirty-three FNABs were performed by cytopathologists after referral from surgeons or oncologists using a 25-gauge or 27-gauge needle. RESULTS: The cytologic diagnosis was negative in 35, atypical in 1, suspicious in 2, and positive for malignant melanoma in 95. Regional lymph node dissections were performed in 78 patients. Of these, 70 positive FNABs were confirmed with no false-positive results. The atypical FNAB was proven positive for malignant melanoma at surgery. Of the two suspicious FNABs, one was confirmed as positive and one showed dermatopathic lymphadenopathy. Of the 35 negative FNAB specimens, 5 patients underwent surgery; 3 FNABs were found to be negative and 2 FNABS were falsely negative. Twenty patients with negative aspirates were followed clinically for 22-45 months (mean, 32 months); 19 patients had no evidence of disease and 1 patient died of disseminated melanoma. CONCLUSIONS: FNAB of palpable lymphadenopathy in patients with malignant melanoma can provide a rapid and accurate assessment of lymph node status and expedite the therapeutic management of these patients.

Lobular capillary hemangiomas: An epidemiologic report, with emphasis on cutaneous lesions.

BACKGROUND: Lobular capillary hemangiomas (pyogenic granulomas) occur on both mucosal and cutaneous surfaces. There are conflicting data regarding the increased prevalence of lobular capillary hemangiomas in female versus male subjects. Some studies have noted a female predominance of lobular capillary hemangiomas, but other studies do not reveal such a disparity. Because of an increased prevalence during pregnancy, oral tumors are also known as "granuloma gravidarum" or "pregnancy tumors." A hormonal influence for these mucosal lesions has been postulated. There are, however, no studies that address a possible relationship between hormones and cutaneous lesions. OBJECTIVE: This study presents the epidemiology of lobular capillary hemangiomas, with an emphasis on cutaneous lesions. METHODS: We reviewed 63,759 dermatopathology reports from a regional, private dermatopathology laboratory and found 325 cases of lobular capillary hemangiomas over a 1-year period. RESULTS: In our study of lobular capillary hemangiomas, cutaneous lesions accounted for 86%, with mucosal lesions representing only 12% of cases. Seven cases were excluded (one was intravascular, two were subcutaneous, and in 4 the location was not specified). Overall, male patients outnumbered female patients. The peak incidence for cutaneous lobular capillary hemangiomas was found in the second decade of life. The most common cutaneous sites were the trunk, upper extremities, and head. Mucosal lesions were primarily seen on the lips, gingiva, and tongue, and these affected females more than males by a ratio of 2:1, most commonly in the fourth decade of life. CONCLUSION: Cutaneous lobular capillary hemangiomas were equally prevalent in male and female patients. This would refute a female hormonal influence in the induction of cutaneous lobular capillary hemangiomas. Our data may suggest a hormonal influence on mucosal lesions because mucosal lobular capillary hemangiomas were twice as common in female patients. However, the small number of lesions in our study precludes us from making such a conclusion.

Invasive carcinoma in clinically suspicious breast masses diagnosed as adenocarcinoma by fine-needle aspiration.

BACKGROUND: Fine-needle aspiration (FNA) biopsy of palpable breast masses along with clinical and radiologic findings can provide rapid distinction between benign and malignant lesions. A preoperative determination of invasive or in situ carcinoma assists in the planning of definitive treatment. Previous studies have concentrated on whether cytologic features adequately distinguish invasion, but to the authors' knowledge the predictive value of clinicopathologic correlation has not been investigated. The authors attempted to determine whether a malignant cytologic diagnosis for a palpable breast mass is sufficient for its definitive surgical management as an invasive neoplasm. METHODS: The authors reviewed 351 FNAs from palpable breast lesions with a cytologic diagnosis of "adenocarcinoma." The presence of invasive disease was determined by histologic demonstration of invasive carcinoma in the corresponding surgical specimen or by identifying metastatic carcinoma in the absence of another primary source. RESULTS: Three hundred forty-three (97.7%) palpable tumors diagnosed as adenocarcinoma by FNA proved to be invasive adenocarcinoma. The remaining eight tumors contained high grade ductal carcinoma in situ, and two of these contained foci suggestive of microinvasion. CONCLUSIONS: A palpable breast mass with an FNA diagnosis of adenocarcinoma usually represents invasive carcinoma. A definitive treatment plan therefore can be planned based on these clinical and FNA findings.

Complications of level I and II axillary dissection in the treatment of carcinoma of the breast.

OBJECTIVE: To assess the complications of level I and II axillary lymph node dissection in the treatment of stage I and II breast cancer, with breast-conservation surgery and mastectomy. SUMMARY BACKGROUND DATA: The role of axillary dissection for staging, and as an effective means of controlling regional nodal disease, has long been recognized. As small and low-grade lesions have been detected more frequently, and as its therapeutic impact has been questioned, axillary dissection has increasingly been perceived as associated with significant complications. METHODS: Two hundred patients, 112 of whom had breast-conservation surgery with axillary dissection and 88 of whom had total mastectomy with axillary dissection, were evaluated 1 year or more after surgery for arm swelling as well as nonedema complications. All patients had arm circumference measurements at the same four sites on both the operated and nonoperated sides. RESULTS: No patient had an axillary recurrence. The mean difference in circumference on the nonoperated versus operated side was 0.425 cm +/- 1.39 at the midbiceps (p < 0.001), 0.315 cm +/- 1.27 at the antecubital fossa (p < 0.001), 0.355 cm +/- 1.53 at the midforearm (p < 0.005), and 0.055 cm +/- 0.75 at the wrist (n.s.). Seven patients (3.5%) had mild swelling of the hand. Heavy and obese body habitus were the only significant predictors of edema on multivariate analysis. One hundred fifty-three (76.5%) patients had numbness or paresthesias of the medial arm and/or axilla after surgery; in 125 (82%) of these, the problem had lessened or had resolved on follow-up assessment. CONCLUSIONS: The characterization of a level I and II axillary dissection as a procedure with significant complications does not appear justified based on this experience.

Different phosphate binding modes of Streptomyces griseus aminopeptidase between crystal and solution states and the status of zinc-bound water.

Phosphate shows a non-competitive inhibition toward a Streptomyces aminopeptidase (sAP) between pH 5.85 (Ki = 0.48 mM) and 9.0 (110 mM), with a pKa of 7.1 likely due to ionization of H2PO4-. This non-competitive inhibition pattern indicates that phosphate binding to sAP in solution is different from that in the crystal structure, where phosphate is bound to the active site Zn(II) ions. Fluoride uncompetitively inhibits sAP from pH 5.5 (Ki = 3.72 mM) to 9.0 (43.6 mM), with a pKa of approximately 6.2 likely due to a coordinated water. The different inhibition natures and pKa values indicate that the two inhibitors bind at different locations.

Irsogladine maleate inhibits angiogenesis in wild-type and plasminogen activator-deficient mice.

BACKGROUND: The activation of the zymogen plasminogen to the serine protease plasmin by urokinase-type (uPA) and tissue-type (tPA) plasminogen activators (PA) is an important event in a variety of physiologic and pathophysiologic processes in mammals. Enhanced PA activity occurs during angiogenesis and has been correlated in vitro and in vivo with increased tumor aggressiveness and is an indicator of poor prognosis in a variety of tumors in humans. Preliminary studies suggest that the antiulcer drug irsogladine maleate (IM) diminishes PA activity in vitro and may inhibit angiogenesis in vivo. To define the precise mechanism of angiogenesis inhibition by IM in vivo, we tested the ability of IM to blunt angiogenesis in a mouse cornea neovascularization model performed in wild-type and PA-knockout mice. METHODS: Three days prior to pellet implantation, groups of C57Bl/6 wild-type, uPA-deficient (upA-/-), and tPA-deficient (tPA-/-) mice received IM (300 mg/kg), IM (500 mg/kg), or vehicle (0.5% carboxymethylcellulose) via oral gavage. After 3 days of treatment, hydron polymer-coated pellets of sucrose aluminum sulfate containing 100 ng of basic fibroblast growth factor (bFGF) were inserted into surgically created pockets in the cornea of each mouse. On postoperative day 6, the neovascularization of each cornea was evaluated by a blinded observer using slit lamp microscopy and photographed. Angiogenesis was quantified by calculating vascular area (mm2) +/- SEM using a modified formula for a half ellipse that incorporates calibrated vessel measurements [Vessel length (mm) x Clock hours x pi x 0.2]. RESULTS: IM treatment (300 and 500 mg/kg/day) resulted in a dose-dependent reduction of angiogenesis in wild-type mice by 21 and 45.3% (P < 0.02, P < 0.001), in tPA-deficient mice by 42.6 and 46% (P < 0.001, P < 0.001), and in uPA-deficient mice by 27.2 and 46% (P < 0.05, p < 0.001), respectively. No quantitative differences in neovascularization were observed in either treatment group between transgenic mouse strains. No toxicity was noted in any group. CONCLUSION: IM inhibits bFGF-induced angiogenesis in wild-type, tPA-knockout, and uPA-knockout mice. The observation that IM significantly diminishes angiogenesis in both PA-deficient mice and wild-type mice suggests that the mechanism of action of IM may be independent of plasminogen activation.

Poly(ADP-ribose) polymerase in human breast cancer: a case-control analysis.

The importance of a genetic polymorphism (A/B allele) of poly(ADP-ribose) polymerase (PARP) pseudogene on chromosome 13q34-qter, and PARP enzyme activities in the development of human breast cancer were evaluated in a cancer case-control study. A total of 309 Caucasian women (> or = 50 years old) were evaluated for the PARP genotype, 70 of whom had histologically confirmed breast cancer, 128 women with benign breast diseases as study controls, and 111 reference controls. Age was significantly associated with case-control status (p < 0.0001), but family history of breast cancer, age at menarche, age at first live birth and parity were not. The frequency of the PARP B allele was similar in breast cancer cases (0.14), study controls (0.13), and reference controls (0.15). In a subset of 14 breast cancer cases and 32 study controls, the mean PARP enzyme activities (induced by H2O2 or oligonucleotide) were observed to be lower in cancer cases; an age-adjusted odds ratio of 3.40 (95% confidence interval = 0.70-19.54) for the below-median oligonucleotide-induced PARP was suggestive of an association. In subjects with the AB or BB genotype, the mean H2O2-induced PARP enzyme activity was significantly higher (p = 0.02, adjusted for case-control status and age) compared with that in subjects with the AA genotype. These findings indicate that: (a) the genetic polymorphism of the PARP pseudogene on chromosome 13 is not associated with the development of breast cancer in our study population; (b) oligonucleotide-induced PARP activity may be useful for identifying postmenopausal women at increased risk for breast cancer; and (c) there is a possible functional link between the genotype of the PARP pseudogene and enzyme activation.

Urokinase-type plasminogen activator-deficient mice are predisposed to staphylococcal botryomycosis, pleuritis, and effacement of lymphoid follicles.

Urokinase-type plasminogen activator (uPA) is thought to be an important mediator in the proteolytic degradation of extracellular matrix components observed in a wide variety of normal physiological and pathological conditions. However, the phenotype of a recently developed strain of urokinase-deficient (uPA-/-) mice appears to be normal when maintained under ideal nonstressful conditions. We report an outbreak of botryomycosis, an unusual staphylococcal infection, in a colony of uPA-deficient mice. A detailed histological examination of these uPA-deficient animals also revealed a variety of previously unreported phenotypic abnormalities such as pleuritis and the effacement of lymphoid follicles in the regional lymph nodes and spleen. Additional phenotypic abnormalities such as dystrophic calcifications and rectal prolapse were also observed in the uPA-deficient population. These abnormalities were also noted in ostensibly healthy uPA-deficient animals. Botryomycosis did not affect a colony of wild-type (uPA+/+) animals maintained concurrently under identical conditions in the same room. The peculiar predisposition of the uPA-deficient animals to this rare bacterial infection and the development of phenotypic abnormalities associated with the targeted disruption the uPA gene suggests that uPA contributes significantly to the cutaneous microenvironment and is additional evidence of the extensive involvement of the plasminogen activators in mammalian physiology.

The management of pigmented lesions of the nail bed.

Pigmented lesions of the nail bed, especially without a history of trauma, represent a diagnostic challenge to the clinician. These lesions are often categorized as melanonychia striata (MS), which refers to any linear tan-brown-black pigmentation of the nail bed. The differential diagnosis of MS includes subungual hematomas, onchomycosis nigricans, junctional nevi, melanoma in situ (MIS), and malignant melanoma (MM). Our algorithm at the New York University (NYU) Medical Center for the treatment of pigmented lesions of the nail bed is presented. A histopathologic diagnosis with any evidence of melanocytic atypia, however subtle, requires absolute confirmation by complete excision. The absence of a clear margin or recurrence requires total nail bed excision and reconstruction using a full-thickness graft. The diagnosis of MIS is similarly treated. The surgical management of subungual MM is discussed. All cases of MM of the hand treated at NYU were reviewed. In all, 30 patients were treated from 1982 to 1995. Follow-up ranged from 6 months to 13 years. In our series, there were 8 cutaneous and 22 subungual melanomas. There was a marked delay in treatment of both groups, with subungual melanomas more often erroneously treated as other pathology prior to correct diagnosis. The 5-year survival rate was 100% for patients with cutaneous lesions, but only 80% for those with the subungual variety. There was a statistical difference in the depths of the lesions (subungual, 3.68 mm; cutaneous, 1.36 mm) with a p-value of 0.008. The role of elective lymph node dissection in the absence of clinical metastases as well as intraoperative sentinel lymphatic mapping remains controversial and is discussed.

Induction of primary cutaneous melanocytic neoplasms in urokinase-type plasminogen activator (uPA)-deficient and wild-type mice: cellular blue nevi invade but do not progress to malignant melanoma in uPA-deficient animals.

Evidence suggests that the plasminogen activators (PAs), in particular urokinase-type PA (uPA), play a pivotal role in tumor invasion and metastasis. We studied the contribution of the PAs to the malignant phenotype through the chemical induction of melanocytic neoplasms in uPA-deficient mice. Primary tumors were induced and promoted concurrently in 35 uPA-/- deficient and 35 uPA+/+ wild-type mice using a single application of 7,12-dimethylbenz(a)anthracene followed by repetitive applications of croton oil. Animals were sacrificed at 60-day intervals for 1 year. At necropsy, the four largest pigmented lesions in each animal were excised, characterized histologically, and evaluated microscopically for evidence of invasion. The regional lymph nodes, lungs, and solid abdominal visceral organs were sectioned and examined microscopically for evidence of metastatic disease. Cellular blue nevi were induced in 100% of uPA-/- and uPA+/+ promoted animals. Although a reduction in the radial and vertical progression of these lesions was noted in the uPA-deficient mice compared with the wild-type group, more than 95% of cellular blue nevi induced in both groups of animals invaded the underlying tissues. These lesions did not metastasize to the regional lymph nodes. Malignant melanoma arose in 5 of 35 (14.3%) of promoted wild-type mice. These tumors were locally aggressive, produced tissue-type PA, but were not metastatic to the regional nodes, lungs, or abdominal viscera. These results indicate that the invasive capability of melanocytic lesions may depend more on tissue-type PA than uPA activity. No melanomas were induced in the uPA-/- mice. The resistance of the uPA -/- strain to melanoma induction suggests that uPA contributes to malignant progression. We propose that the absence of uPA negatively affects tumorigenesis by decreasing the liberation and availability of growth factors such as basic fibroblast growth factor.

Stereotactic fine-needle aspiration biopsy for the evaluation of nonpalpable breast lesions: report of an experience based on 2,988 cases.

BACKGROUND: The increasing use of mammography has led to a significant increase in the detection of clinically occult lesions, the majority of which prove to be benign. SFNB has been suggested as a means of expediting a diagnosis for lesions that are malignant while limiting surgical biopsies for those that are benign. METHODS: Clinically occult mammographic lesions were assessed by SFNB in 2,988 patients. Definitive histologic diagnoses were made on surgical specimens in all instances in which the cytologic diagnosis was malignant, suspicious, or atypical. Patients with benign cytology were either followed with interval mammograms or underwent surgical biopsy. RESULTS: Two hundred ninety-one of the 295 lesions (99%) diagnosed as cancer via SFNB were confirmed by histopathology. Twenty-two of the 22 lesions (100%) that were diagnosed as suspicious were diagnosed on histopathology as malignant. Forty-three of the 70 lesions (61%) with cytologic atypia were diagnosed on histopathology to be malignant. CONCLUSIONS: SFNB is an accurate means of diagnosing carcinoma, but must be followed by surgical biopsy when the cytology shows atypia. For lesions diagnosed as benign by SFNB, close interval mammography is essential.

Sinus histiocytosis mimicking metastatic melanoma in lymph nodes of a patient with a large joint prosthesis: case report and review of the literature.

Malignant melanoma metastases to regional lymph nodes may be mimicked by several non-neoplastic processes, including sinus histiocytosis induced by fragments shed from joint prostheses. A patient who had an elective lymph node dissection for malignant melanoma and was found to have "post-prosthesis lymph node histiocytosis" resembling metastatic disease is described. Knowledge of the patient's past history of a total shoulder joint replacement along with the use of polarized light microscopy to identify birefringent particles of prosthetic debris allows for an accurate histologic diagnosis.

Management considerations for melanonychia striata and melanoma of the hand.

This article discusses the diagnosis and management of pigmented lesions of the hand, especially the nail bed.

Improved survival of patients with melanoma with an antibody response to immunization to a polyvalent melanoma vaccine.

BACKGROUND: Melanoma vaccine treatment appears to slow the progression of melanoma in some patients, particularly in patients in whom it stimulates cellular antimelanoma immune responses. The relationship of vaccine-induced antibody responses to clinical outcome is less clear. The purpose of this study was to investigate the clinical relevance of antibody responses to melanoma vaccine immunization. METHODS: Eighty-two evaluable patients with surgically resected American Joint Committee on Cancer Stage III malignant melanoma were immunized to a partially purified, polyvalent, melanoma antigen vaccine. Antimelanoma antibodies were measured by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis before vaccine treatment and 1 week after the fourth immunization. RESULTS: Vaccine treatment induced or augmented antibody responses to melanoma in 32 (39%) of the patients. The antibodies were directed to one or more antigens of 38-43, 75, 110, 150 and/or 210 kDs, which previously have been shown to be expressed preferentially in cultured human melanoma cells. The median disease free survival of patients with a vaccine-induced antibody response to one or more of these antigens was 5.4 years compared with 1.4 years for nonresponders (P = 0.06), and 5-year overall survival was 71% compared with 44%, respectively (P = < 0.01). As determined by Cox multivariate analysis, the difference in overall survival was independent of disease severity or of immunologic competence as evaluated by ability to be sensitized to dinitrochlorobenzene. The difference in survival between antibody responders and nonresponders improved with time. CONCLUSIONS: The antibody response to vaccine treatment is an immune marker of vaccine activity that appears to be predictive of a later reduction in the recurrence of melanoma and is unrelated to the vaccine's ability to induce cellular immune responses. This finding suggests that vaccine treatment may be effective in slowing the progression of melanoma in some patients and that the protective effect is mediated partly by vaccine-induced antimelanoma antibodies.