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Biomedical subjects

D W Fortune

Publications and source records attributed to D W Fortune.

At least 19 recordsLinked to original sources

Expression of insulin-like growth factor binding protein-3 (IGFBP-3) in the psoriatic lesion.

Epidermal hyper-proliferation is a key feature of psoriasis, and a role for IGF-I in this process has previously been proposed. Herein we investigated the expression of IGF binding proteins in the psoriatic lesion and compared it with normal skin. With in situ hybridization, we found that IGFBP-3 mRNA was expressed in the basal layer of the epidermis in normal skin. IGFBP-3 was also detected immunohistochemically, exclusively in the basal layer. In the psoriatic lesion, IGFBP-3 mRNA was similarly limited to the basal layer despite the characteristic expansion of the basaloid keratinocyte compartment and was detected only in the suprapapillary epidermis, where IGFBP-3 mRNA was more abundant than in normal or uninvolved epidermis, and IGFBP-3 protein could be readily detected with specific antibody. As with IGFBP-3 mRNA, which represents the likely site of IGFBP-3 synthesis, IGFBP-3 was strictly limited to the basal keratinocytes of the suprapapillary epidermis. By using an antibody to the cell cycle antigen Ki67, we also showed that the suprapapillary epidermis, where IGFBP-3 expression was maximal, contained few keratinocytes undergoing mitosis, whereas the tips of the rete pegs, where IGFBP-3 expression was conspicuously absent, contained many keratinocytes undergoing mitosis. We suggest that IGFBP-3 is a growth inhibitor in basal keratinocytes and that absence of IGFBP-3 in the tips of rete pegs may contribute to epidermal hyper-proliferation in the psoriatic lesion.

Adult↗

Intravenous leiomyomatosis of the uterus: a clinicopathologic study of 22 cases.

Twenty-two cases of intravenous leiomyomatosis (IVL) of the uterus were examined at the Royal Women's Hospital, Melbourne, within a 22-year period. The mean age of the patients was 46 years (range, 23-66). Nine patients presented with a pelvic mass, nine with abnormal uterine bleeding, and one with prolapse of the uterus. In three cases, the presenting features were unknown. Surgical exploration confirmed the presence of a uterine mass (mean size, 7.8 cm) which in seven cases extended into the broad ligament. In only 11 cases was involvement of the myometrial vessels obvious on gross examination. However, no extension into the iliac veins or inferior vena cava was found. In seven cases, the tumor involved to a minimal degree the immediately adjacent or contiguous myometrial veins, and the diagnosis of IVL was made incidentally on microscropic examination. Of the 16 patients with follow-up (mean, 7.5 years) all are now disease free. Five years after the diagnosis of IVL, one patient (case 10) had a pulmonary smooth-muscle tumor resected. All 22 patients were treated by surgery alone, and to date none have died from disease. Our findings support the benign biologic behavior of IVL even in the presence of metastases.

Adult↗

Human papillomavirus vulvitis: a new disease or an unfortunate mistake?

OBJECTIVE: To determine whether human papillomavirus (HPV) was responsible for symptoms in women with vulvar pruritus, pain and superficial dyspareunia who had been referred with a diagnosis of HPV vulvar disease made on clinical and/or colposcopic and/or histological grounds. DESIGN: In addition to standard clinical and laboratory investigations of the whole population, a sample of 15 test cases from the population of 71 women referred with a clinicopathological diagnosis of HPV vulvar disease, and two positive and 21 negative controls were assayed for HPV DNA. Polymerase chain reaction assays using L1 consensus primers were performed blinded to the clinicopathological diagnosis. SETTING: Dermogynaecology Clinic at Mercy Hospital for Women. SUBJECTS: Seventy-one women referred with a diagnosis of HPV vulvar disease. RESULTS: Thirteen cases which could be tested for HPV DNA were negative. Diagnoses other than HPV were found for the women's presentation in all cases. CONCLUSIONS: In the population studied, our investigations indicated that the clinicopathological diagnosis of HPV infection was incorrect and that HPV was not a cause of vulvar symptoms. We believe that the term HPV vulvitis is unfortunate as it has invited destructive treatments and drawn attention away from more likely causes of this difficult group of vulvar conditions.

Adolescent↗

Percutaneous ultrasound guided uterine needle biopsy.

OBJECTIVE: To determine the safety, accuracy and usefulness of percutaneous ultrasound guided uterine needle biopsy. SETTING: Transabdominal uterine biopsy was performed with an ultrasound directed biopsy gun. The biopsy was performed as an outpatient procedure under local anaesthesia. MAIN OUTCOME MEASURES: The safety, accuracy and clinical value of the procedure; a comparison of the clinical and ultrasound diagnoses with the biopsy and surgical histological diagnoses; and the effect of the biopsy result on the choice of treatment by the surgeon and patient. RESULTS: There were no complications. Accuracy was validated in all seven patients who subsequently had surgical procedures and more extensive myometrial histological investigation. Biopsy diagnosis improved clinical diagnosis in nine of the ten patients, and altered or assisted in the ultrasound diagnosis in eight of the ten patients. Decisions concerning choice of treatment by the doctor or patient were assisted by the biopsy result in seven patients. CONCLUSION: Percutaneous ultrasound guided uterine needle biopsy is a useful procedure in the diagnosis of myometrial disease.

Adult↗

Pathogenesis of megalourethra.

Idiopathic megalourethra in infants is an enlargement of the pendulous urethra with no evidence of distal obstruction. Two aborted fetuses at 14 and 19 weeks of gestational age exhibited megalourethra with definite complete distal obstruction. The urethras of these 2 fetuses were studied histologically confirming the presence of an uncanalized epithelial core in the glans obstructing the lumen of the patent urethra. Embryologically, this epithelial core is normal but early canalization achieves continuity with the lumen of the penile urethra. In these 2 fetuses canalization was arrested or delayed with complete obstruction of the urethra in the glans and dilatation of the pendulous urethra. In living children with this form of megalourethra the urethra of the glans is patent. Canalization of the epithelial core in the glans of the survivors may have been delayed rather than arrested and may be a cause of megalourethra.

Congenital Abnormalities↗

Rectal adenocarcinoma with germ cell elements treated with chemotherapy.

A patient with adenocarcinoma of the rectum containing germ cell elements in the form of endodermal sinus tumor and choriocarcinoma is described, believed to be the first such tumor reported in the literature. The serum levels of alpha-fetoprotein and human chorionic gonadotropin were markedly elevated. The source of the markers was localized to the neoplastic tissue by the immunoperoxidase technique. The patient developed extensive hepatic metastases thought to be due to choriocarcinoma for which she received chemotherapy. One wk after commencing treatment a massive fatal hepatic hemorrhage occurred.

Adenocarcinoma↗

Ligneous (pseudomembranous) inflammation of the female genital tract. A report of two cases.

Two women, aged 28 and 32, presented with primary infertility and severe dysmenorrhea. The younger woman developed recalcitrant and recurrent firm vaginal, cervical and possibly endometrial lesions over a period of six years; the older patient had similar material in the cervix, endometrium and a fallopian tube. The lesions were composed of amorphous eosinophilic hyaline or necrotic material, shown by histochemical and immunoperoxidase stains to be partly fibrin. Pathologic examination showed that the lesions were similar to those of ligneous (pseudomembranous) conjunctivitis, a rare disease that may occasionally affect the lower female genital tract. However, neither patient had eye disease, and ligneous conjunctivitis has not previously been reported to involve the upper genital tract. Endometrial and tubal involvement could readily explain primary infertility and dysmenorrhea in these patients.

Adult↗

Cervical cancer--what role for human papillomavirus?

OBJECTIVE: To review the role of human papillomavirus (HPV) as a causative agent of cancer of the cervix. DATA SOURCES, data synthesis, study selection: Medical journals, recently published text books related to cancer of the cervix and HPV and Papillomavirus Reports were examined to review the pathology of cervical cancer and its precursor lesions, its epidemiology in Australia and overseas, methods of detection of HPV (in particular molecular biology techniques used to diagnose HPV) and evidence linking HPV with genital neoplasia. CONCLUSION: While there is compelling evidence strongly linking certain HPV types with genital cancer, a causative role is yet to be proven and the aetiology is most likely multifactorial. Detection and typing of high risk genotypes of HPV in the genital tract as a diagnostic exercise to identify those women most at risk of developing genital neoplasia is not currently recommended.

Female↗

The clinicopathological features of three babies with osteogenesis imperfecta resulting from the substitution of glycine by valine in the pro alpha 1 (I) chain of type I procollagen.

The features of three babies with perinatal lethal osteogenesis imperfecta (OI II) resulting from substitutions of glycine by valine in the triple helical domain of the alpha 1(I) chain of type I collagen were studied. The babies were heterozygous for this substitution at residue 1006 in case 1 (OI35), 973 in case 2 (OI59), and 256 in case 3 (OI7B). OI35 had the most severe clinical form, OI IIC, with premature rupture of membranes, severe antepartum haemorrhage, stillbirth, severe short limbed dwarfism, and extreme osteoporosis. OI59 was a better formed baby but was also born prematurely as a result of premature rupture of membranes and severe antepartum haemorrhage. She had the radiographic features of OI IIA. OI7B was born at term and also had the radiographic features of OI IIA. Pathological examination of the skeletons of OI35 and OI59 showed grossly deficient intramembranous and endochondral ossification. Trabecular bone was sparse in the long bones and vertebrae. The trabeculae contained a cartilage core and an overlying layer of woven bone or osteoid. The diaphyses lacked cortical bone. The periosteal fibroblasts of OI35 contained grossly distended rough endoplasmic reticulum consistent with the 53% reduction in collagen secretion by cultured dermal fibroblasts. The aorta, skin, and lungs were hypoplastic in OI35 and OI59. The findings in this study show that glycine substitutions by valine in Gly-X-Y triplets, from glycine 256 to glycine 1006, of the triple helical domain of alpha 1(I) chains produce the OI II phenotype. The phenotype was most severe in the baby with the most carboxy-terminal substitution.

Adult↗

Pathology of the vulva.

Increasing agreement is being reached among the International Society for the Study of Vulvar Disease, the International Society of Gynecological Pathologists, the World Health Organization, and the International Federation of Gynecology and Obstetrics concerning the terminology used to describe the abnormalities of and surgical procedures for vulvar disease. This paper focuses on Paget's disease of the vulva, which is beset with recurrence and a higher incidence of invasive disease than previously recognized, although diagnostic methods have improved. Agreements on the definition for and measurement of superficially invasive squamous cell carcinoma of the vulva have also been reached. The prognostic features of tumors likely to be associated with nodal metastases are being delineated with a view to the use of conservative surgery. The risks in underestimating a tumor's capacity to metastasize are emphasized.

Carcinoma, Squamous Cell↗

Arteriovenous malformations of the uterus.

Six cases of the rare condition of arteriovenous malformation of the uterus are reported. Uterine bleeding was the most common presentation, with the site of the lesion and the caliber of the vessels determining its degree. A preoperative diagnosis was made by angiography in two patients, and was aided by ultrasonography in one.

Adult↗

Steroid receptors and ovarian tumors: variation within primary tumors and between primary tumors and metastases.

Estrogen and progesterone receptors have been measured in primary and secondary ovarian carcinoma in eight patients, in bilateral ovarian tumors in 16 patients, and from multiple sites within the same tumor in 16 patients (12 primary and 4 secondary). In the majority of cases, metastatic tumors contained less receptors than their primary tumors. Marked variations in receptor content were noted within the same tumor and between bilateral tumors. This variation in receptor levels may explain the discrepancy between the presence of receptors and the response to hormonal treatment. Multiple sites of ovarian carcinoma need to be assayed for receptor content before a final decision can be made on receptor status.

Female↗

Fibroepithelial polyps with atypical stromal cells (pseudosarcoma botryoides) of vulva and vagina. A report of 13 cases.

Thirteen cases of female genital tract fibroepithelial polyps containing atypical stromal cells are described, eight arising from the vulva, a site of origin not previously reported. These tumours must be differentiated from sarcoma botryoides, which they resemble both grossly and microscopically. Although fibroepithelial polyps are benign, two of our cases recurred after incomplete excision.

Adult↗

The role of second-look laparotomy in the management of patients with ovarian carcinoma.

Second-look laparotomy has been performed on 76 patients with ovarian carcinoma each of whom was clinically free of tumour after completing a programme of postoperative chemotherapy (60 patients), pelvic radiotherapy followed by chemotherapy (14 patients) or observation (2 patients). The initial stage, bulk of residual tumour, completion of hysterectomy and bilateral salpingo-oophorectomy and an interval of 11 months or more between diagnosis and second-look surgery were all significantly (p less than .05) associated with negative findings. Recurrences occurred after a negative operation in 10 of 42 (23.8%) patients and were more frequent amongst patients with grade 3 tumours (p = .03). Macroscopic cancer was found in 23 (30.3%) patients and microscopic cancer in 11 (14.8%) patients. Survival was related to the surgical findings and to the amount of residual tumour at the conclusion of the second-look operation. Survival of patients with no macroscopic residue (those found to have microscopic tumour and those who had complete excision of macroscopic tumour) was significantly longer than that of patients with macroscopic residue (median survival 38.2 versus 19.0 months, p = .01). These results suggest that benefit from second-look laparotomy is confined to patients with microscopic or totally resectable tumour for whom second-line therapy may still be curative.

Adenocarcinoma↗

Hepatotoxicity and death following two enflurane anaesthetics.

A 67-year-old woman died with massive fatty change in the liver 41 hours after her second enflurane anaesthetic in 28 days. The clinical features of five previously reported similar deaths are summarised. Possible mechanisms of the hepatotoxicity are reviewed briefly.

Aged↗

Occult fetomaternal haemorrhage as a cause of fetal mortality and morbidity.

Spontaneous fetomaternal haemorrhage is an important, but usually overlooked, cause of perinatal mortality and morbidity. Although fetomaternal bleeding in the third trimester of pregnancy is common it is normally less than 0.1 ml. A fetal macrotransfusion (greater than 5 ml) is uncommon, but is important because it is insidious, unexpected and usually occurs in completely normal pregnancies. This paper analyses the perinatal mortality and morbidity associated with occult fetomaternal haemorrhage at the Royal Women's Hospital, Melbourne. It may lead to fetal distress before and during labour, unexplained stillbirth, or nonhaemolytic neonatal anaemia. A Kleihauer test on maternal blood will readily detect fetomaternal bleeding, and we describe a simple way of calculating the absolute volume of fetal red cells present. Greater awareness of the problem may eventually lead to diagnosis sufficiently early to permit effective treatment.

Adult↗

Low malignant potential tumors of the ovary: a study of 76 cases.

This study analyzes the clinical and pathological features of 76 patients who were diagnosed as having ovarian low malignant potential tumor over a 20-year period: 39 (51.3%) of the tumors were mucinous, 29 (38.2%) serous, three (3.9%) endometrioid, and five (6.6%) mixed. Patients with serous tumors were significantly younger (mean age 40 years) than those with mucinous tumors (mean age 50.5 years). Serous tumors were more frequently bilateral (48.3%) than mucinous tumors (12.8%). The extent of tumor (FIGO stage) at the primary laparotomy was related to the prognosis: the survival of 14 patients with stage III and six patients with stage II tumor was significantly inferior to that of the 56 patients with stage I tumors (P less than .01). Patients with stage III mucinous low malignant potential tumors and pseudomyxoma peritoneii fared badly. Four patients with stage II and 13 patients with stage III tumors had residual tumor after primary surgery. Five of these patients received no subsequent treatment of whom four are alive and well from 5.5 to 19 years after diagnosis. Three patients received pelvic radiotherapy. Eleven patients were treated with chemotherapy for residual or recurrent tumor but only one (9.1%) had an unequivocal response.

Adult↗