Lennart Boquist

A one-year multicenter study of efficacy and safety of a continuous, low-dose, estradiol-releasing vaginal ring (Estring) in postmenopausal women with symptoms and signs of urogenital aging

OBJECTIVE We studied the efficacy, safety, and acceptability of an estradiol-releasing (6.5 to 9.5 micrograms per 24 hours) silicone vaginal ring (Estring) in postmenopausal women with symptoms and signs of urogenital aging during a treatment period of 1 year. STUDY DESIGN The study was open with blind analysis of vaginal cytologic testing. In addition to gynecologic examination, subjective symptoms were assessed and vaginal pH and urinary samples (for bacteriuria) were obtained before insertion of Estring. This procedure was repeated every 3 months up to 1 years treatment, together with requests concerning acceptability and adverse experiences. At inclusion and end of Estring treatment, vaginal smears for evaluation of cytologic results were obtained. RESULTS Estring induced a high maturation value in the vaginal mucosa and restored vaginal pH to levels normality seen in fertile women (< 5.5). For most variables a 90% responder rate (proportion of cured and improved patients) was found after 3 months and up to 1 year regarding subjective symptoms and objective signs of vaginal mucosal atrophy. Twenty-eight (20%) of 136 women, withdrew from the study, 8 (6%) of them because of adverse events. Three women reported vaginal bleeding, none associated with malignancy or endometrial proliferation. Ten (7%) reported vaginal irritation, and in two cases vaginal ulcers were found. About 90% did not remove the ring during any of the 3-month treatment periods, and 78% used the four consecutive rings continuously up to 1 year. The ring was given a strong preference (p < 0.001) by patients with previous experience of other administration forms. CONCLUSION Estring represents a safe, highly effective, and very well-accepted administration form for long-term treatment of urogenital disorders caused by estrogen deficiency in postmenopausal women.

Prognostic factors in chondrosarcoma. A comparative study of cellular DNA content and clinicopathologic features

In a retrospective study of 45 surgically treated chondrosarcomas, the prognostic significance of the cellular DNA content and different clinicopathologic factors was analyzed both separately and in combination. The relationship between these parameters was also investigated. Diploid (normal DNA content) chondrosarcomas were associated with a significantly (P ≤ 0.001) higher ten‐year survival rate than hyperploid (abnormally increased DNA content) chondrosarcomas. Apart from ploidy, factors such as tumor size, tumor location and tumor grade also proved to be of prognostic importance. However, patients with diploid tumors had a better prognosis than those with hyperploid tumors, almost regardless of location, size, grade or even treatment. Nevertheless, additional prognostic information could be obtained by combining ploidy with size, location and grade of the tumors. Ploidy and treatment were significantly related to the ten‐year recurrence rate. No statistical relationship could be demonstrated between ploidy and other prognostic factors. A strong correlation (P ≤ 0.001) was, however, found between location and size of the tumors. Thus, distal tumors were significantly smaller and, moreover associated with a better prognosis than axial tumors. The results indicate that ploidy probably is the best predictor of the clinical course in chondrosarcoma. While tumor location and size may be assumed to determine the conditions for radical surgery, ploidy and grade seem to reflect the inherent biological malignancy in chondrosarcoma. Consideration of all these factors seems to provide not only valuable prognostic information, but also guidelines for treatment.

Primary carcinoma of the appendix.

Primary adenocarcinoma of the appendix is rare and less than 200 cases are on record. The present material consisted of 20 cases collected from different hospitals. The cases are described in respect of sex and age-distribution, symptoms, treatment and prognosis. Of 7 patients with malignant mucocele, 6 subjected to appendectomy only, were still alive 5 years after the operation. Of 12 patients with colonic type of adenocarcinoma, 3 had been treated with appendectomy only. Of these, 2 were still alive 5 years after the operation. The remaining 9 patients had undergone right hemicolectomy. Only one of them was alive 5 years after the operation. A compilation of a further 39 cases garnered from the literature, however, showed that 60% had survived at least 5 years after right hemicolectomy, compared with 46% after appendectomy alone. Appendectomy alone is probably a sufficiently radical operation for malignant mucocele provided the tumor has not grown through the submucosa and that it is confined to the tip of the appendix. Right hemicolectomy is indicated for the colonic type of adenocarcinoma.

A comparative multicenter study of the effects of continuous low-dose estradiol released from a new vaginal ring versus estriol vaginal pessaries in postmenopausal women with symptoms and signs of urogenital atrophy

OBJECTIVE Our purpose was to study the efficacy, safety, and acceptability of a new estradiol-releasing (6.5 to 9.5 micrograms per 24 hours) silicone rubber vaginal ring compared with Ovesterin 0.5 mg estriol vaginal pessaries. STUDY DESIGN Gynecologic clinical status, vaginal pH, cytologic characteristics, and occurrence of bacteriuria were determined before starting and after 3 and 12 weeks of treatment in 146 postmenopausal women. RESULTS Both treatments alleviated the subjective and objective symptoms of estrogen deficiency excellently, and both were equally effective at restoring the vaginal pH to levels normally seen in fertile women (< 5.5). Vaginal cytologic studies showed a significant difference in maturation value in favor of the estradiol-releasing silicone rubber vaginal ring, as measured by the pathologists assessment of the proliferation of the vaginal mucosa. A total of 77% of users were classified as responders, compared with 39% in the pessary group. Both treatments were well accepted. The administration of the pessary was associated with a significantly higher (p < 0.001) incidence of discomfort than that of the ring, which was given better (p < 0.001) rating by the patients at the 12-week visit. A strong preference (p < 0.001) for the ring was shown by patients with previous experience with pessaries. CONCLUSION Treatment of urogenital symptoms in postmenopausal women with an estradiol-releasing vaginal ring is shown to be an effective and safe method, exhibiting advantages over treatment with estriol vaginal pessaries.

Ultrastructure of pancreatic acinar and islet parenchyma in rats at various intervals after duct ligation.

Im Rattenpankreas kommt es nach einer Gangligatur zu einer Degeneration und Atrophie der Acinusepithelien. Das zugrunde gegangene Drüsenparenchym wird durch Fett- und Bindegewebe ersetzt. Zeichen einer Regeneration der Acinusepithelien lassen sich nicht beobachten. Die B-Zellen des Inselsystems zeigen in den ersten postoperativen Tagen eine Degranulierung und eine Schwellung des endoplasmatischen Reticulum sowie des Golgikomplexes. Außerdem treten degenerative Veränderungen und auch Nekrosen einzelner B-Zellen auf. Die übrigen Zellen des Inselsystems zeigen keine Veränderungen. An den Ductuli lassen sich Zellproliferationen, Mitosen und Gruppen von agranulären oder granulierten Zellen beobachten, welche sich zu Inselkomplexen entwickeln. Die Ursache für die B-Zellveränderungen und die anschließende Neubildung von Inselzellen werden diskutiert. Duct ligation of rat pancreas evoked degeneration and atrophy of the acinar cells. The atrophied parenchyma was replaced by adipose and fibrous tissue. No signs of regeneration of acinar cells were observed. The islet β-cells showed degranulation and prominent endoplasmic reticulum and Golgi complex the first post-operative days. There were also degenerative changes and even necrosis of some β-cells. In the other islet parenchymal cells no obvious lesions were found. The ductules seemed to proliferate and showed mitoses and buds composed of agranular and granulated cells which appeared to develop into islets. The cause for the β-cell lesions and the subsequent neoformation of islet cells is discussed.

Osteopenia in mice with genetic diabetes

Bone mass and growth were studied in mice with genetic diabetes (db/db) characterized by obesity, hyperinsulinemia and hyperglycemia, in their lean litter mates (db/+) and in non-diabetic mice of the same strain (+/+). No significant difference was observed between db/+ and +/+ mice. The length, bone mass, bone mineral mass, bone mineral density and content of moisture of the tibia of the db/db mice were significantly decreased compared with the db/+ and +/+ mice. Microradiographs of the distal femur diaphysis of the db/db mice showed a significant reduction of the spongious bone area and of the number and thickness of bone trabeculae with a normal mineralization. The amount of osteoid was significantly increased in the db/db mice. The area of cortical bone of the tibia epiphysis of the db/db mice was significantly decreased compared with the db/+ and +/+ mice. The data suggest the occurrence of osteopenia due to decreased mineralization in mice with genetic diabetes.

Primary malignant melanoma of the central nervous system

SummaryAmong 10 patients with primary malignant melanoma of the CNS, the tumour was localized to the brain in 7 cases (group I) and to the spinal cord in the remaining 3 cases (group II). A mean age of about 50 years and a male preponderance were found. In group I there were various neurological symptoms, and cerebral arteriography disclosed either vascular or non-vascular lesions. Diagnosis was made at light microscopic examination of material obtained at operation or autopsy. The tumour was either diffuse or localized and involved both the leptomeninges and cerebral parenchyma. After operation the patients survived for between 2 weeks and 7 months. In group II there were compression symptoms and pathological gas myelography. At operation tumours were found that involved the leptomeninges and medulla. Light microscopic examination showed malignant melanoma. The postoperative survival was longer (12 months-2 years and 9 months) than in group I.

Cilia in normal and regenerating islet tissue

SummaryCiliated cells occasionally occur in pancreatic ductule cells and islet β-cells of normal Chinese hamsters. In the regenerating pancreatic parenchyma of alloxan-treated Chinese hamsters an increased amount of cilia is observed in the ductule cells and islet β-cells. No obvious cilia were found in the other pancreatic cell types of normal and alloxan-treated animals. One and the same ductule cell possesses one, two, or rather often many cilia protruding into the ductule lumen. In the islet β-cells there are one or two cilia that often extend into intercellular spaces. The fibre arrangement varies in different parts of the cilia. The basic fibre pattern seems to be 9 + 2, the 9 peripheral fibres consisting of 2 subfibres, and the 2 central being single. The basal bodies (centrioles) consist of 9 groups of 2 or 3 aligned tubular elements. Filaments are associated with the centrioles. The functional significance of the cilia is discussed.

Giant-cell tumors of the spine and sacrum causing neurological symptoms.

Pain and neurological disturbances were the most frequent symptoms in patients with giant-cell tumors of the spine (4 cases) and sacrum (1 case). A good prognosis is possible in patients with vertebral tumor localization. There were no recurrences at follow-up 6 to 16 years after the first admission. The patient with a sacral tumor is alive more than 15 years after the first admission with some remaining neurological symptoms. Early surgical and/or radiation therapy is important. If institution of treatment is delayed more than three months after the onset of nerve root symptoms, there is a great risk of development of irreversible neurological lesions.

A novel spontaneous metastasis model of human osteosarcoma developed using orthotopic transplantation of intact tumor tissue into tibia of nude mice

Evaluation of potential new treatment strategies requires adequate experimental tumor models which resemble the clinical situation as closely as possible. The purpose of the present study was to establish a new human osteosarcoma spontaneous metastasis model using orthotopic transplantation of histologically intact tumor tissue into the tibia of nude mice. Intact tumor pieces, obtained from the 32nd serial passage of subcutaneously growing human osteosarcoma xenografts, were implanted into the proximal tibia in 31 nude mice. Animals were sacrificed and autopsied 2, 4, 6, and 8 weeks after transplantation and examined macroscopically and microscopically for local tumor growth and metastases. All mice developed local intratibial bone tumors that were radiographically and histologically similar to primary human osteosarcoma. Lung metastases were observed in all mice, local and distant lymph node metastases in 15 (48%), and liver metastases in 6 (19%) mice. The microscopic appearance of the metastases was similar to that observed in the donor patientÕs tumor, corresponding subcutaneous xenografts and orthotopically transplanted intratibial tumors. This spontaneous metastasis model of human osteosarcoma in nude mice may resemble a clinical situation and could thus be useful for studies on local tumor growth, metastasis formation and therapy.