Diagnostic SOX10 gene signatures in salivary adenoid cystic and breast basal-like carcinomas.

BACKGROUND: Salivary adenoid cystic carcinoma (ACC) is an insidious slow-growing cancer with the propensity to recur and metastasise to distant sites. Basal-like breast carcinoma (BBC) is a molecular subtype that constitutes 15-20% of breast cancers, shares histological similarities and basal cell markers with ACC, lacks expression of ER (oestrogen receptor), PR (progesterone receptor), and HER2 (human epidermal growth factor receptor 2), and, similar to ACC, metastasises predominantly to the lung and brain. Both cancers lack targeted therapies owing to poor understanding of their molecular drivers. METHODS: Gene expression profiling, immunohistochemical staining, western blot, RT-PCR, and in silico analysis of massive cancer data sets were used to identify novel markers and potential therapeutic targets for ACC and BBC. For the detection and comparison of gene signatures, we performed co-expression analysis using a recently developed web-based multi-experiment matrix tool for visualisation and rank aggregation. RESULTS: In ACC and BBC we identified characteristic and overlapping SOX10 gene signatures that contained a large set of novel potential molecular markers. SOX10 was validated as a sensitive diagnostic marker for both cancers and its expression was linked to normal and malignant myoepithelial/basal cells. In ACC, BBC, and melanoma (MEL), SOX10 expression strongly co-segregated with the expression of ROPN1B, GPM6B, COL9A3, and MIA. In ACC and breast cancers, SOX10 expression negatively correlated with FOXA1, a cell identity marker and major regulator of the luminal breast subtype. Diagnostic significance of several conserved elements of the SOX10 signature (MIA, TRIM2, ROPN1, and ROPN1B) was validated on BBC cell lines. CONCLUSION: SOX10 expression in ACC and BBC appears to be a part of a highly coordinated transcriptional programme characteristic for cancers with basal/myoepithelial features. Comparison between ACC/BBC and other cancers, such as neuroblastomaand MEL, reveals potential molecular markers specific for these cancers that are likely linked to their cell identity. SOX10 as a novel diagnostic marker for ACC and BBC provides important molecular insight into their molecular aetiology and cell origin. Given that SOX10 was recently described as a principal driver of MEL, identification of conserved elements of the SOX10 signatures may help in better understanding of SOX10-related signalling and development of novel diagnostic and therapeutic tools.

Mutational screening of the CD40 ligand (CD40L) gene in patients with X linked hyper-IgM syndrome (XHIM) and determination of carrier status in female relatives.

AIMS: To analyse the gene encoding the CD40 ligand (CD40L) in 11 Australian patients from 10 unrelated families with the X linked hyper-IgM (XHIM) phenotype. METHODS: The CD40L gene was screened for mutations using direct sequencing of exon specific polymerase chain reaction (PCR) products. RESULTS: Ten mutations were identified. Seven of these mutations have been described previously, whereas three new nonsense mutations were identified, namely: E108X (c.322G>T), G167X (c.499G>T), and C218X (c.654C>A). Ten of 15 female family members revealed both a mutated allele and a normal allele, indicating that they were XHIM carriers. CONCLUSION: The 10 mutations (including the three new ones) identified in this study reflect the heterogeneity of the CD40L gene, and indicate the need for accurate and reliable molecular testing of those patients suspected of XHIM.

Hashimoto's thyroiditis with papillary thyroid carcinoma (PTC)-like nuclear alterations express molecular markers of PTC.

AIMS: Focal papillary thyroid carcinoma (PTC)-like nuclear alterations have been documented in Hashimoto's thyroiditis; however, the molecular association between PTC and Hashimoto's thyroiditis is poorly understood. The aim of this study was to determine whether molecular expression patterns of PTC are present in association with PTC-like nuclear alterations in Hashimoto's thyroiditis. METHODS AND RESULTS: The expression of four genes known to be up-regulated in PTC [LGALS3 (galectin3), CITED1, KRT19 (cytokeratin 19) and FN1 (fibronectin-1)] and the human mesothelial cell protein identified by monoclonal antibody HBME1 was evaluated. Immunohistochemistry was performed on 23 cases of Hashimoto's thyroiditis with focal or diffuse Hürthle cell change and PTC-like nuclear alterations, 37 PTC and 18 normal thyroids. Focal expression of galectin3 (GAL3), CITED1, cytokeratin 19 (CK19), HBME1 and fibronectin-1 (FN1) was seen in 87%, 65%, 43%, 26% and 17% of Hashimoto's thyroiditis, respectively, only in thyrocytes showing PTC-like nuclear alterations. In contrast, diffuse expression of GAL3, CITED1, CK19, HBME1 and FN1 was seen in 100%, 95%, 70%, 87% and 89% of PTC, respectively. Normal thyroid tissues did not express any of these proteins. Following immunohistochemistry, four Hashimoto's thyroiditis cases were found to contain foci of PTC. These foci were highlighted by the diffuse and strong expression of PTC-associated proteins, which prompted additional retrospective scrutiny of the haematoxylin and eosin-stained sections leading to appreciation of complete PTC-type nuclear atypia. CONCLUSIONS: Focal PTC-like immunophenotypic changes in Hashimoto's thyroiditis suggest the possibility of early, focal premalignant transformation in some cases of Hashimoto's thyroiditis.

Assessment of male CVID patients for mutations in the Btk gene: how many have been misdiagnosed?

The presentation of hypogammaglobulinaemia in young males without a family history of immunodeficiency can pose a diagnostic problem. In the past, the presence of B-cells has suggested a diagnosis of common variable immunodeficiency (CVID), although genotypic analysis has now clarified that individuals with B cells may have mutations in their Btk gene. In order to address the issue of how many male individuals with a clinical diagnosis of CVID do in fact have mutations in the Btk gene, we analysed a group of 24 male patients. Single-strand conformation polymorphism (SSCP) analysis was used to screen the patient cohort for mutations in the Btk gene. Given the size of the Btk gene, the number of patients in the cohort and the amount of available DNA, multiplex PCR reactions were utilized to span the 19 exons and promoter region of the gene. Where abnormal migration patterns were observed with multiplex PCR reactions, in nine of the 24 patients, the individual Btk gene fragments were re-amplified and analysed again by SSCP. Following this analysis, four patients continued to demonstrate abnormal SSCP migration patterns. However, direct sequencing of the relevant Btk gene fragments for these four CVID patients revealed a mutation in only one patient. The mutation was the previously described polymorphism at position 2031 of Btk gene within exon 18. These results indicate that caution should be taken with the application of SSCP analysis to mutation detection. While it has a role to play in screening large patient cohorts, direct sequencing is a necessary adjunct to such analysis. Finally, the clinical diagnosis of CVID in this cohort successfully excluded males with Btk mutations.

Expression of melanocytic differentiation markers in malignant melanomas of the oral and sinonasal mucosa.

Malignant melanomas of the oral and sinonasal mucosa are rare tumors. Amelanotic variants can, on occasion, be difficult to recognize by routine light microscopy. Immunohistochemical studies may be needed for a final diagnosis. A number of new monoclonal antibodies to melanocytic differentiation antigens have been studied recently on primary cutaneous and metastatic melanoma. However, little is known about these antibodies for the diagnosis of mucosal melanomas. In this study the authors analyzed 79 oral and sinonasal mucosal melanomas of 65 patients. A total of 35 tumors originated from the oral mucosa (21 primary tumors, eight local recurrences, and six metastases) and 44 melanomas were from the sinonasal tract (27 primary tumors, nine local recurrences, and eight metastases). Immunohistochemical studies were performed on paraffin-embedded tissues, using the following antibodies: anti-S-100 protein, T311 (anti-tyrosinase), A103 (anti-Mart-1/Melan-A), D5 (antimicrophthalmia-associated transcription factor), and HMB-45 (anti-gp100). Of 35 oral mucosal tumors, 34 (97%) were positive with anti-S-100 protein, 33 (94%) with T311, 30 (85%) with A103, 26 (74%) with D5, and 25 (71%) with HMB-45. All five desmoplastic melanomas of the oral mucosa were positive for S-100 protein, four for tyrosinase, and one each for HMB-45 and A103. No desmoplastic melanoma was positive with D5. All 44 sinonasal melanomas were positive for tyrosinase and Mart-1/Melan-A (100%). Forty-three (98%) were positive with HMB-45, 42 (95%) with anti-S-100 protein, and 40 (91%) with D5. These results reveal that T311 is the most sensitive marker for sinonasal melanomas and closely approaches the sensitivity of anti-S-100 protein for oral mucosal melanomas. For desmoplastic mucosal tumors, anti-S-100 protein remains the most sensitive marker.

Are microinvasion and micrometastasis in breast cancer mountains or molehills?

BACKGROUND: The increased rate of early detection of breast cancer due to widespread mammographic screening has led to an increased incidence of in situ as well as microinvasive carcinoma. The enhanced pathological examination to which sentinel lymph nodes are subjected has led to an increased rate of detection of micrometastatic carcinoma. Despite the augmented rate of diagnoses of both diseases, the pathological diagnoses as well as clinical management of these entities continue to be controversial. DATA SOURCES: A computerized literature search was performed on the Medline and PubMed database from 1990 to date. Relevant earlier publications were also perused. The database of the Department of Pathology at New York Presbyterian Hospital-Well Medical College of Cornell University were also accessed. CONCLUSIONS: Based on cumulative data, patients diagnosed with either microinvasive or micrometastatic carcinoma of breast have a relatively favorable, albeit guarded, prognosis. Treatment recommendations for both of these disease entities continue to be controversial, and may remain so until additional refined clinicopathological data becomes available.

Preoperative chemoradiation and coloanal J pouch reconstruction for low rectal cancer.

Our objective was to determine clinical outcomes of treatment of low rectal adenocarcinoma with neoadjuvant chemoradiation, rectal excision, and coloanal J pouch reconstruction. A retrospective review of 69 patients with stage B2 or higher lesions was performed. Preoperative chemoradiation was followed by low anterior resection and coloanal J pouch anastomosis, with end loop ileostomy. Data were analyzed using the SPSS computer software. There were 46 males and 23 females, with a median age of 63 years. Pathologic staging showed no tumor in the specimen, i.e.: stage 0, 14 per cent; stage A, 14 per cent; stage B, 53 per cent; stage C, 18 per cent; and stage D, 1.4 per cent. Postoperative mortality was 2.8 per cent, and the pelvic leak rate was 4.3 per cent. After curative resection, 89 per cent patients are alive and 83 per cent are disease free with a mean follow-up of 50 months. The local recurrence rate is 7.2 per cent. Nodal status was the most important predictor of survival and disease-free survival. Most (96%) have fewer than two bowel movements a day and are satisfied with the functional results. We conclude that preoperative chemoradiation and coloanal J pouch reconstruction can achieve low recurrence rates and prolonged survival for most patients with low rectal cancer with an acceptable quality of life.

Microinvasive carcinoma (T1mic) of the breast: clinicopathologic profile of 21 cases.

Clinicopathologic data on microinvasive carcinoma of the breast (MICB) as defined by the 1997 TNM criteria (T1mic < or = 1 mm) is scarce. Histologic slides of 109 cases from 1993 through 1997, in which microinvasion was either suspected or diagnosed initially, were reviewed. A double immunoenzyme-labeling technique using antismooth muscle actin and anticytokeratin antibody on the same section was used to confirm invasion in equivocal cases. All foci of invasion were measured by ocular micrometer. Twenty-one cases were confirmed to be MICB. The mean age of the patients was 60.9 years. Thirteen patients presented with mammographic abnormalities on routine examination (60.9%). MICB was ductal in 18 patients, including one tubular carcinoma, and was lobular in three patients. The mean number of invasive foci was two per patient (range, one to seven foci). The accompanying duct carcinoma in situ had high-grade nuclei and necrosis in 16 of 18 patients (89%), 13 of which (72%) were comedo-type. Two of the 15 patients had one positive axillary lymph node each (13.3%). Eleven patients underwent mastectomy, nine received radiation therapy, one received chemotherapy, and two underwent lumpectomy only. Median follow up was 28 months (range. 18-63 months). One patient had a chest wall recurrence of infiltrating duct carcinoma and another recurred with duct carcinoma in situ.

Microinvasive carcinoma of the breast: can it be diagnosed reliably and is it clinically significant?

Deciding whether in-situ breast carcinoma is associated with microinvasion is a common problem. Histological features resembling invasion can be simulated by in-situ carcinoma distorted by inflammatory and reparative changes. Having expended the effort to diagnose genuine microinvasion, just how useful is this diagnosis in planning further treatment and follow-up? In the following articles, Hoda et al. comment on the utility of immunohistochemistry in resolving uncertainty about the presence of microinvasion, and Ellis et al. critically appraise the definition of microinvasion and its clinical significance.

Double immunolabeling with cytokeratin and smooth-muscle actin in confirming early invasive carcinoma of breast.

Histopathological identification of invasive breast carcinoma in its earliest phases is fraught with pitfalls. Preinvasive malignant lesions complicated by radial scar, sclerosing adenosis, and lobular cancerization, among other lesions, may simulate invasive carcinoma. Fibrosis, inflammatory reaction, and other stromal changes around in situ carcinoma may mask microinvasive foci on routine stains. Conventional immunohistochemistry to demonstrate basement membrane or myoepithelial cell layer may not, by itself, be unequivocally diagnostic of invasion. We performed a novel double immunoenzyme labeling technique using an avidin-biotin complex peroxidase-diaminobenzidine system for smooth-muscle actin followed by an alkaline phosphatase anti-alkaline phosphatase-new fuchsin system for cytokeratin antigen on formalin-fixed, paraffin-embedded histology sections to evaluate 32 such problematic cases. The initial histologic impression with hematoxylin and eosin staining alone was as follows-first group: microinvasive carcinoma-10; second group: carcinoma in situ--"stromal invasion cannot be ruled out"--15; third group: frankly infiltrating carcinoma of various grades and morphologic types-6. The last group served as positive control for invasion. One fibroadenoma with fine-needle-aspiration-induced artifact simulating stromal invasion was also included. The double immunoenzyme labeling technique imparted a dark brown color to the myoepithelial cells and a vivid red color to the epithelial cells, making individual or loosely cohesive groups of malignant epithelial cells infiltrating the stroma easily detectable, whereas their in situ counterparts were contained within dark brown myoepithelial boundaries. The TNM 1997 definition of pT1mic, i.e., extension of malignant cells in the stroma with no focus measuring >0.1 cm, was followed to classify microinvasion. In the first group, microinvasion was confirmed in six cases but was not demonstrable in four. In the second group, definite invasion was identified in five cases, ruled out in nine, and in one case the suspicion of early invasion could not be entirely ruled out even after double immunoenzyme labeling. Thus, it was possible to render a definite opinion regarding presence or absence of invasion in 24 of 25 (96%) cases diagnosed as or suspected to be microinvasive. The precise and simultaneous elucidation of topography between malignant cells and myoepithelial cells on a single permanent section makes this technique a useful diagnostic tool in the evaluation of those cases of breast carcinoma that exhibit equivocal invasion.

Pulmonary immunocytoma with massive crystal storing histiocytosis: a case report with review of literature.

An unusual immunocytoma (lymphoplasmacytoid lymphoma) composed predominantly of sheets of globoid and spindle-shaped crystal-storing histiocytes was detected incidentally in the right lung of a 72-year-old woman. Scattered lymphoplasmacytic aggregates within the tumor had monoclonality with anti-kappa immunoglobulin (Ig) M antibodies. The crystals were outlined positively by the same antibodies. They stained an intense blue with phosphotungstic acid-hematoxylin (PTAH) and were found during electron microscopy to be membrane bound and also within type I pneumocytes and the extracellular space. Excessive production of kappa IgM by neoplastic low-grade lymphoplasmacytoid cells of B-cell origin in an altered intra- or extracellular milieu may lead to crystallization and phagocytosis by reactive histiocytes. Review of the literature revealed seven more cases: four in the head and neck, and one each in the skin, the lymph node, and the lung. IgM was the most frequently crystallizing immunoglobulin (four of seven) and all had kappa light chains. The lesion needs to be differentiated from neoplastic and nonneoplastic histiocytic and lymphoplasmacytic disorders. The difference with bronchial mucosa-associated lymphoid tissue lymphoma and marginal zone lymphoma is, perhaps, semantic.

Observations on the histopathologic diagnosis of microinvasive carcinoma of the breast.

Our histopathologic criteria for diagnosing microinvasive carcinoma of the breast may be enunciated as follows: (1) cytologically malignant cells in the stroma associated with in situ carcinoma, (2) absence of basement membrane and myoepithelial cells around the invasive cells, (3) frequent accompanying stromal alterations in the form of myxomatous change and loosening of connective tissue, and (4) the frequent presence of an inflammatory cell infiltrate composed of lymphocytes and plasma cells. Most or all of these four features are present in cases of ductal microinvasive carcinoma of the breast, but the lobular type is not likely to be accompanied by stromal changes or a lymphoplasmacytic cell infiltrate. The minimum information regarding microinvasive carcinoma of the breast that should be conveyed in the final pathology report includes size as measured by the ocular micrometer or a statement that microinvasion refers to a lesion smaller than 1 mm, the number of foci of invasion, and the spatial distribution of the invasive foci. The nuclear grade of the invasive cells and the size, type, and nuclear grade of the accompanying DCIS should be specified. The status of margins, presence of vascular channel involvement (a rarity in microinvasive carcinoma of the breast), and degree of proliferative changes in adjacent nonneoplastic breast tissue should be reported. Immunostains for basement membrane and myoepithelial cells may be helpful in the diagnosis of microinvasive carcinoma of the breast. Sclerosing lesions such as radial scar and sclerosing adenosis can simulate microinvasive carcinoma of the breast, especially when the latter is associated with in situ carcinoma. Caution should be exercised in cases wherein in situ malignant cells may be dislodged by needling procedures or during dissection of the excised specimen. Cautery-induced artifacts also hinder optimal histologic assessment. In some cases, it is virtually impossible to determine if true invasion is present, and the statement "microinvasive carcinoma of the breast cannot be entirely excluded" may be employed as a last resort. We consider the latter diagnosis to be the last refuge of the diligent pathologist and do not recommend it unless all diagnostic measures, including examination of deeper levels and supplemental stains, have been exhausted. It may be necessary to seek an expert opinion in "difficult" cases, particularly in the event that therapeutic decisions are to be based on the determination of invasion. From a clinical perspective, the management of microinvasive carcinoma of the breast ought to be dictated by the individual circumstances in each case. Based on currently available data, which admittedly suffer from lack of diagnostic uniformity, the vast majority of patients with microinvasive carcinoma of the breast will be node-negative and can look forward to an excellent prognosis. It is hoped that since the UICC has adopted a previously recommended definition of microinvasive carcinoma of the breast, prospective or retrospective studies with uniform diagnostic criteria will be conducted that will enable more definitive conclusions regarding the treatment and prognosis of microinvasive carcinoma of the breast.

Management of recurrent rectal prolapse.

PURPOSE: Many operations have been described for the management of rectal prolapse. Despite an overall recurrence rate of greater than 15 percent, few reviews address how to deal with this problem. This report summarizes our experience with recurrent rectal prolapse and includes suggestions for reoperative management of failed repairs from both abdominal and perineal approaches. PATIENTS AND METHODS: Fourteen patients (3 male) ranging in age from 22 to 92 (mean, 68) years underwent operative correction of recurrent rectal prolapse. Average time from initial operation to recurrence was 14 (range, 6-60) months. Initial operations (before recurrence) were as follows: perineal proctectomy and levatorplasty (10), anal encirclement (2), Delorme's procedure (1), and anterior resection (1). Operative procedures performed for recurrence were as follows: perineal proctectomy and levatorplasty (7), sacral rectopexy (abdominal approach; 3), anterior resection with rectopexy (2), Delorme's procedure (1), and anal encirclement (1). Average length of follow-up was 50 (range, 9-115) months. RESULTS: No further episodes of complete rectal prolapse were observed during this period. Preoperatively, three patients were noted to be incontinent to the extent that necessitated the use of perineal pads. The reoperative procedures failed to restore fecal continence in any of these three individuals. One patient died in the postoperative period after anal encirclement from an unrelated cause. CONCLUSION: Surgical management of recurrent rectal prolapse can be expected to alleviate the prolapse, but not necessarily fecal incontinence. Perineal proctectomies can be safely repeated. Resectional procedures may result in an ischemic segment between two anastomoses, unless the surgeon can resect a previous anastomosis in the repeat procedure. Nonresectional procedures such as the Delorme's procedure should be strongly considered in the management of recurrent rectal prolapse if a resectional procedure was performed initially and failed.

Class I HLA antigens in two long-separated populations: Melanesians and South Amerinds.

Class I HLA antigens have been compared in 5,835 Melanesians of Papua New Guinea and 2,028 Amerindians of South America. The sample includes 50 PNGMel ethnolinguistic groups and 22 SAmInd groups. Both carry 15 serologically defined antigens and an undefined C allele. Except for A2 in Papua New Guinea and Cw1 in South America, these antigens are widely distributed in their respective populations. Nine (A2 and A24, B39, B60 and B62, and Cw1, Cw3, Cw4, and Cw7) are common to both. This commonality suggests that these two populations derive from an ancestral population with less polymorphism than modern East Asians. In both populations several theoretically possible haplotypes were absent, and other haplotypes were in positive disequilibrium in both. The parallels in disequilibria suggest that haplotypes are subject to selective forces acting on the level of allelic interaction. Based on three locus haplotype frequencies, the PNGMel groups form five clusters with internally typical linguistic and geographic characteristics and miscellaneous category, but SAmInd groups show no cluster.

Perineal sigmoidectomy for sigmoid procidentia: report of a case.

Although rectal procidentia is not an uncommon disease, presentation of more proximal segments of the large bowel through the anus is extremely rare. We report a male patient with an acute sigmoid prolapse secondary to a large villous adenoma acting as the lead point. Since the prolapsed segment was irreducible and exhibited signs of vascular compromise, an intraoperative colonoscopy and perineal sigmoidectomy with a primary anastomosis was carried out. Postoperatively, the patient did well and was discharged 5 days after his operation. Recognition of the difference between sigmoid and rectal procidentia should influence the surgeon's choice of operation, along with the viability of the prolapsed bowel and overall condition of the patient.

Solitary intracranial plasmacytoma of the skull base.

Two cases of extradural solitary plasmacytoma (SIP) with infiltration of the dura, destruction of the skull base, multiple cranial nerve palsies and proptosis are presented. The cases were treated aggressively with surgery and radiotherapy and showed no signs of progressing to multiple myeloma after 15 months and four and a half years respectively.

Role of the seton in the management of anorectal fistulas.

PURPOSE: To identify the incidence of major fecal incontinence and recurrence after staged fistulotomy using a seton. METHODS: A five-year retrospective chart review of 116 patients (70 males and 46 females) ranging in age from 18 to 81 years (mean, 42 years), in whom setons were placed as part of a surgical procedure for anorectal fistulas, was carried out. Follow-up ranged from 2 to 61 months (mean, 23 months). RESULTS: Setons were employed to identify and promote fibrosis around a complex anorectal fistula as part of a staged fistulotomy in 65 patients (56 percent). Other indications for seton placement included 24 women with anteriorly situated high transsphincteric fistulas (21 percent) and three patients with massive anorectal sepsis (floating, freestanding anus) (2.5 percent). In addition, setons were used to preclude premature skin closure and promote controlled long-term fistula drainage in 21 patients with severe anorectal Crohn's disease (18 percent) and in three patients with AIDS (2.5 percent). Major fecal incontinence (requiring the use of a perineal pad) occurred in five patients (5 percent), and recurrent fistulas were noted in three (3 percent). CONCLUSIONS: Staged fistulotomy using a seton is a safe and effective method of treating high or complicated anorectal fistulas.

Arthritis in the highlands of Papua New Guinea.

Acute polyarthritis is an important cause of morbidity in many tropical countries. Classification has often been difficult, with the term tropical polyarthritis used for those in whom a diagnosis could not be made. The implication that this is a distinct entity is probably incorrect, with likely causes being septic arthritis or post-infective reactive arthritis. This study aimed to determine the types of arthritis found in 43 patients (30 men) presenting consecutively to the Goroka Base Hospital in the Eastern Highlands of Papua New Guinea. Gonococcal arthritis was diagnosed in eight patients (six men) on the basis of isolation of Neisseria gonorrhoeae from the joint aspirate. In all cases the N gonorrhoeae was identified by the closed culture system on chocolate agar, but not always by routine plating. There were no specific clinical features that identified patients with a gonococcal septic arthritis. The remaining 34 patients had an undifferentiated oligoarthritis. The pattern of arthritis in men and women was of a lower limb pauciarticular arthritis with a predilection for the knee and ankle joints. A total of 30% of male patients had a history of urethral discharge and 44% of all patients had preceding diarrhoea. Arthritis was the only feature in 59% of patients and in 32% there was an associated enthesitis. In this study most patients had an oligoarthritis consistent with a reactive arthritis or a septic arthritis due to N gonorrhoeae. Broth inoculation of synovial fluid was the best method to isolate N gonorrhoeae, with standard methods for gonococcal isolation failing in some patients. It is recommended that the term 'tropical polyarthritis' is no longer used as it does not refer to a specific entity but consists of several known arthritides.

Ayurvedic agents produce differential effects on murine and human melanoma cells in vitro.

This study was performed to evaluate the relative efficacy of Maharishi Amrit Kalash ambrosia (MAK-5) and Maharishi Amrit Kalash nectar (MAK-4) on murine (B-16) and human (SK-Mel) melanoma cells in culture. Ethanol extract (EE) of MAK-5 (EE-MAK-5) induced morphological differentiation (enlargement of soma and nuclei and formation of long dendritic processes) and growth inhibition in mouse melanoma cells, whereas EE-MAK-5 inhibited only growth in human melanoma cells. Murine melanoma cells were more sensitive (about 3 times) than human melanoma cells in culture to EE-MAK-5; the aqueous extract (AE) of MAK-5 (AE-MAK-5) was ineffective in both cells. Boiling EE-MAK-5 for 10 minutes or exposing it to light at room temperature for 72 hours did not alter growth-inhibiting potency. Ethanol extract of another herbal agent, MAK-4 (EE-MAK-4), inhibited growth in human melanoma cells but not in mouse melanoma cells. AE-MAK-4 was ineffective for both cells. These results suggest that murine and human melanoma cells respond differently to MAK-5 and MAK-4 and that human melanoma growth-inhibiting agents are present in both EE-MAK-5 and EE-MAK-4.