Adenoid Cystic Carcinoma of the Bartholin's Gland: A Diagnostic Dilemma.

Adenoid cystic carcinomas of the Bartholin's gland are extremely rare and are often misdiagnosed. There are currently no definite treatment guidelines. This article describes the case of a 33-year-old female who was managed at our centre for adenoid cystic carcinoma of the Bartholin's gland. She presented with a prolonged history of a vulvar lesion which was eventually diagnosed as adenoid cystic carcinoma of the Bartholin's gland. She was subsequently treated with wide local excision of the primary and inguinal lymph node dissection followed by adjuvant radiotherapy and chemotherapy. She had gross perineural invasion on MRI imaging. The present case highlights the diagnostic dilemma in this extremely rare cancer and the literature further explores the natural history and treatment options.

Olanzapine-induced Pancytopenia: A Rare but Worrying Complication.

Unlike clozapine, and despite its structural similarities, olanzapine is not usually associated with haematological suppression. Nonetheless this case report highlights an incident of olanzapine-induced thrombocytopenia and neutropenia in a first-contact patient. We report on a 50-year-old male who presented with 7 years of delusions and hallucinations. A diagnosis of schizophrenia was made in the absence of any suggestive features of mood disorders, substance abuse or organicity, and olanzapine as second-line treatment. Within a week of starting treatment he developed biochemical neutropenia and thrombocytopenia without any clinical symptoms that resolved after cessation of the offending drug. An organic workup for infective, inflammatory, and neoplastic causes was unremarkable. Comparison with other case reports and 3 postulated mechanisms are discussed. Despite its comparative rarity, the addition of this case report to a growing corpus suggests that clinicians should maintain heightened surveillance of patients prescribed olanzapine, to identify any untoward iatrogenic haematological abnormalities or immunosuppression.

Small-molecule inhibition of CBP/catenin interactions eliminates drug-resistant clones in acute lymphoblastic leukemia.

Drug resistance in acute lymphoblastic leukemia (ALL) remains a major problem warranting new treatment strategies. Wnt/catenin signaling is critical for the self-renewal of normal hematopoietic progenitor cells. Deregulated Wnt signaling is evident in chronic and acute myeloid leukemia; however, little is known about ALL. Differential interaction of catenin with either the Kat3 coactivator CREBBP (CREB-binding protein (CBP)) or the highly homologous EP300 (p300) is critical to determine divergent cellular responses and provides a rationale for the regulation of both proliferation and differentiation by the Wnt signaling pathway. Usage of the coactivator CBP by catenin leads to transcriptional activation of cassettes of genes that are involved in maintenance of progenitor cell self-renewal. However, the use of the coactivator p300 leads to activation of genes involved in the initiation of differentiation. ICG-001 is a novel small-molecule modulator of Wnt/catenin signaling, which specifically binds to the N-terminus of CBP and not p300, within amino acids 1-110, thereby disrupting the interaction between CBP and catenin. Here, we report that selective disruption of the CBP/ß- and γ-catenin interactions using ICG-001 leads to differentiation of pre-B ALL cells and loss of self-renewal capacity. Survivin, an inhibitor-of-apoptosis protein, was also downregulated in primary ALL after treatment with ICG-001. Using chromatin immunoprecipitation assay, we demonstrate occupancy of the survivin promoter by CBP that is decreased by ICG-001 in primary ALL. CBP mutations have been recently identified in a significant percentage of ALL patients, however, almost all of the identified mutations reported occur C-terminal to the binding site for ICG-001. Importantly, ICG-001, regardless of CBP mutational status and chromosomal aberration, leads to eradication of drug-resistant primary leukemia in combination with conventional therapy in vitro and significantly prolongs the survival of NOD/SCID mice engrafted with primary ALL. Therefore, specifically inhibiting CBP/catenin transcription represents a novel approach to overcome relapse in ALL.

Megestrol acetate therapy and secondary adrenal suppression.

BACKGROUND: Adrenal suppression has been noted in patients who are receiving medroxyprogesterone acetate (MPA). Megestrol acetate (MA) is used to treat patients with advanced breast carcinoma, cachaexia related to acquired immune deficiency syndrome, and disseminated carcinomatosis, and it is believed to have fewer side effects than MPA. The aim of this study was to test for secondary adrenal suppression in patients receiving MA therapy for advanced metastatic cancer. METHODS: Ten postmenopausal female patients receiving long term MA therapy, nine with advanced metastatic breast carcinoma and one with metastatic ovarian carcinoma, were recruited consecutively from the oncology outpatient clinic at Ninewells Hospital in Dundee, Scotland. A short synacthen test and a corticotrophin-releasing hormone (CRH) stimulation test were performed on two separate occasions. Urine collection for 24-hour urinary free cortisol was performed on 6 patients. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (T4) were measured in eight patients. An insulin stress test (IST) was performed on two patients. RESULTS: Nine of 10 patients had a poor cortisol response to the short synacthen test. The CRH test had abnormal results in eight of nine patients. In all patients tested, 24-hour urinary free cortisol excretion was low, indicating adrenal suppression. Basal serum FSH, LH, TSH, and free T4 values indicated normal pituitary function. Adrenocorticotrophic hormone response in the CRH test varied and is discussed in this article. CONCLUSIONS: MA causes secondary adrenal suppression that is thought to be due to its effect at the hypothalamic level. The authors recommend a short course of steroid replacement for patients receiving MA at times of acute illness.

Isolation of Entamoeba histolytica from arthritic knee joint.

Amoebae were isolated from an arthritic knee of a male patient. The organisms grew in Egg Yolk Infusion medium, and in Diamond's Biosate Iron-Serum-33 medium, which contained Trypanosoma cruzi, and were identified microscopically as Entamoeba histolytica. Furthermore, amoebae-like organisms in aspirate and cultures were immunocytochemically identified using monoclonal antibodies against E. histolytica. On the basis of the morphologic and immunologic observations, it was concluded that the knee lesion was caused by infection with E. hystolytica. The knee lesion resolved following treatment with metronidazole. This case is the first report of an amoebic infection of the knee joint.

Growth and milk intake of exclusively breast-fed Myanmar infants.

Twenty-nine exclusively breast-fed infants from moderate and low socio-economic groups were followed-up from birth to 6 months of age. Breast milk intake and body weight of the infants were measured at monthly intervals and morbidity recorded. It is interesting to note that although the mean birth weight of 2.76 kg was only 85 per cent of the NCHS reference standard, catch-up growth occurred whereby the exclusively breast-fed infants attained 94 per cent and 101 per cent of the reference standard at 1 and 2 months of age respectively. At 3 months of age, the mean weight of the infants was 99 per cent of the reference standard and then the growth curve began to falter between 4 and 5 months of age, from 97 per cent at 4 months to 93 per cent of the reference standard at 5 months, the mean weight increment (kg/month) between 4 and 5 months being (less than -1 SD) of the reference value. On the other hand, milk intake of these infants increased from 453 g/d at 1 month to 621 g/d at 4 months reaching a value of 655 g/d at 5 months. It was also observed that the morbidity pattern did not seem to differ, especially at 3-4 months and 4-5 months. The faltering of growth between 4 and 5 months of age was probably due to the fact that the increase in breast milk intake was not sufficient to meet the increase in nutritional requirements needed for the growth of these infants after the age of 4 months.

Otomycosis in Burma, and its treatment.

Otomycosis of the auditory canal is common in Burma. Of 346 cases of otitis externa seen in a hospital outpatient clinic during two consecutive rainy seasons, 189 were due to fungus infection. Aspergillus species were the fungi isolated most frequently. Infection was most commonly due to self-manipulation. Itching and tinnitus were common complaints. Treatment by local cleansing and application of antifungal agents was effective, 10% 5-fluorocytosine ointment being most successful.