Alendronate treatment for osteoporosis: a review of the clinical evidence.

Bisphosphonates have recently gained an increasing role in the management of osteoporosis. The aminobisphosphonate, alendronate has recently been introduced as a new agent for the treatment of postmenopausal osteoporosis. This paper reviews the clinical evidence for the use of this agent and seeks to assess its place in osteoporosis management.

Effect of cell density on the expression of adhesion molecules and modulation by cytokines.

Little is known about the regulation of integrin expression. Using flow cytometry, we have characterized the expression of integrin subunits and other adhesion molecules in bladder and colonic cell lines and studied their modulation by the cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). We show that although TNF-alpha and IFN-gamma may modulate integrin expression, these effects are, in the case of some integrin subunits, secondary to cytokine-induced changes in cell density.

Vitamin D intoxication causes hypercalcaemia by increased bone resorption which responds to pamidronate.

Objective: Vitamin D intoxication is a relatively rare but treatable cause of hypercalcaemia. In the past this has been undertaken using corticosteroids. Previous observations have suggested that there is increased bone resorption in hypervitaminosis D.

Phase II trials of rhizoxin in advanced ovarian, colorectal and renal cancer.

Rhizoxin is a tubulin-binding anti-neoplastic agent which is active in a range of murine tumour models. The recommended schedule, of intravenous (i.v.

Loss of cyclin-dependent kinase inhibitor genes and chromosome 9 karyotypic abnormalities in human bladder cancer cell lines.

Loss of cell cycle control through the structural or functional aberration of checkpoint genes and their products is a potentially important process in carcinogenesis. In this study, a panel of well-characterised established human bladder cancer cell lines was screened by the polymerase chain reaction for homozygous loss of the cyclin-dependent kinase inhibitor genes p15, p16 and p27. The results demonstrate that, whereas there was no genetic loss of p27, homozygous deletion of both p15 and p16 genes occurred in seven of 13 (54%) independent bladder cell lines tested.

The acute phase protein response in patients receiving subcutaneous IL-6.

IL-6, tumour necrosis factor-alpha (TNF-alpha) and IL-1 are thought to be the key mediators of the acute phase response although much of the evidence is based on in vitro studies. It is not clear to what extent each of the acute phase proteins are regulated in vivo by each of these cytokines. The aim of this study was to examine the effects of IL-6 treatment in eight patients with cancer on the concentrations of an extensive range of positive and negative acute phase proteins.

Interferon-alpha and survival in renal cell cancer.

Objective: To establish whether the use of interferon-alpha might result in improved survival, using two large series of patients with advanced renal cell cancer treated during studies of chemotherapy and biological therapy, respectively.

Patients And Methods: Patients treated either in the Eastern Cooperative Oncology Group (ECOG) chemotherapy protocols (327 patients) or in protocols employing interferon as part of a European randomized study or phase II studies at the Norwegian Radium Hospital (231 patients) were retrospectively analysed. Groups for comparison were matched by exclusion of those with an ECOG performance status > 2, no prior nephrectomy, brain metastases or prior chemotherapy.

Patterns of splice variant CD44 expression by normal human urothelium in situ and in vitro and by bladder-carcinoma cell lines.

CD44 core and splice variant exon expression was investigated in the stratified transitional epithelium of the urinary tract and in normal and malignant bladder epithelial cell lines in vitro. Antibodies against core CD44 epitopes and splice exon variants v3, v4/5, v5 and v6 showed an intense reaction in the basal and lower intermediate urothelial cell layers, which was consistently lost from the upper intermediate and superficial cell layers. Seven independent cell lines established from normal human urothelium expressed complex multiple-spliced CD44 mRNA transcripts when tested by RT-PCR and were positive with antibodies against CD44 core epitopes and splice variants v3, v4/5, v5 and v6.

Cytokeratin 20 expression by non-invasive transitional cell carcinomas: potential for distinguishing recurrent from non-recurrent disease.

Although approximately 50% of patients with non-invasive (Ta) papillary transitional cell carcinoma show no recurrence of their disease, current histopathological approaches cannot distinguish this sub-group from those patients in whom the disease will recur. In this 5 year retrospective study, we have shown that cytokeratin 20 (CK20) was expressed in 19 of 29 (65.5%) of non-invasive papillary tumours of grades 1 or 2.

Cyclophosphamide: review of its mutagenicity for an assessment of potential germ cell risks.

Cyclophosphamide (CP) is used to treat a wide range of neoplastic diseases as well as some non-malignant ones such as rheumatoid arthritis. It is also used as an immunosuppressive agent prior to organ transplantation. CP is, however, a known carcinogen in humans and produces secondary tumors.

Molecular and phenotypic characterization of a new mouse insertional mutation that causes a defect in the distal vertebrae of the spine.

We have identified and characterized the phenotype of a new insertional mutation in one line of transgenic mice. Mice carrying this mutation, which we have designated TgN(Imusd)370Rpw, display undulations of the vertebrae giving rise to a novel kinky-tail phenotype. Molecular characterization of the insertion site indicates that the transgene integration has occurred without any substantial alterations in the structure of the host sequences.

Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma.

Purpose: Sixty patients with metastatic melanoma were treated in a phase II study with the imidazotetrazine derivative temozolamide to assess further the efficacy demonstrated in previous phase I studies.

Patients And Methods: Fifty-five of 56 eligible patients were assessable for toxicity and 49 for response. The patients received temozolomide 150 mg/m2/d over 5 successive days orally (total dose, 750 mg/m2) in the first course.

Hydroxyproline excretion is increased in diabetes mellitus and related to the presence of microalbuminuria.

Increased fracture frequency and low bone mass have each been reported in patients with diabetes. To see if these were related to increased bone resorption we have measured the urinary excretion of hydroxyproline in 73 patients with Type 1 (insulin-dependent) diabetes, 67 patients with Type 2 (non-insulin-dependent) diabetes, and 75 control subjects. Hydroxyproline excretion was increased in both types of diabetes: Type 1: 21 (10-36) (median (IQR) mumol mmol creatinine-1; Type 2: 25 (13-43) mumol mmol creatinine-1; control: 10 (6-22) mumol mmol creatinine-1 (p < 0.

Evaluation of the efficacy of the VEEP regimen in adult Hodgkin's disease with assessment of gonadal and cardiac toxicity.

Purpose: The aim of this phase II study was to investigate the potential of the vincristine, epirubicin, etoposide, and prednisolone (VEEP) regimen to reduce the risks of long-term sequelae of chemotherapy such as sterility, cardiopulmonary damage, and second malignancies, while maintaining efficacy in terms of response and survival.

Patients And Methods: Eighty-five adult patients with newly diagnosed and previously untreated stage II to IV Hodgkin's disease (HD) were entered and monitored for a minimum of 1 year. Patients were treated to maximum response plus two further courses, and if they had not attained a complete response (CR) or CR-unconfirmed/uncertain [CR(u)] were changed to second-line chemotherapy.

Soluble forms of the adhesion molecule E-cadherin in urine.

The adhesion molecule E-cadherin is essential for maintaining epithelial intercellular adhesion. Loss or reduced expression of E-cadherin has been related to invasive behaviour in a wide range of carcinomas. Using immunoblotting techniques, the existence of multiple soluble forms of E-cadherin was demonstrated in urine from healthy volunteers and patients with benign urinary tract disorders or bladder cancer.

Detection of epithelial cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction.

Circulating cancer cells in the blood play a central role in the metastatic process. Their number can be very small and techniques for their detection need to be both sensitive and specific. Polymerase chain reaction (PCR) has been successfully used to detect small numbers of tumour cells in haematological cancer in which abnormalities in DNA are sufficiently consistent to make this possible.

Preliminary in situ identification of estrogen target cells in bone.

Although estrogens profoundly influence skeletal growth and maturation, their mechanism of action is still unclear. To identify their target cells in bone, estrogen receptors were located by immunofluorescence using the H222 monoclonal antibody in cryosections (both undecalcified and briefly decalcified) of hyperplastic mandibular condyle (persistent asymmetric mandibular growth) from a 14-year-old girl and radius and ulna from an 18-month-old female pig (epiphyseal fusion) and from a 3-month-old guinea pig (epiphyses open). Bone was removed from the animals at the peak of estrus.

Osteopenia, neurological dysfunction, and the development of Charcot neuroarthropathy.

Objective: To determine factors that might be associated with the development of Charcot neuroarthropathy.

Research Design And Methods: This cross-sectional prevalence study examined neurological function and bone density in matched groups of neuropathic diabetic patients with and without radiological evidence of Charcot neuroarthropathy.

Results: Patients with Charcot neuroarthropathy had a global impairment of neurological function that was significantly greater than that of otherwise matched non-Charcot neuropathic patients.

The relationship of cancer pain to anxiety.

The interaction between pain and anxiety in the setting of somatic illness is a widely recognised association. More accurate knowledge about the association and also about the means of assessing anxiety in a clinical setting are of use to the clinician. The present study used the Hospital Anxiety and Depression Scale for assessment of anxiety, and the set of linear analogue scales for detecting the presence and severity of anxiety and pain in an oncology clinic, where patients were undergoing active treatment for cancer.

Early clinical evaluation of neuroblastoma cell detection by reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosine hydroxylase mRNA.

Disseminating disease in neuroblastoma is of considerable clinical importance. Detection of circulating neuroblastoma cells using tyrosine hydroxylase (TH) as a tissue-specific target for reverse transcriptase-polymerase chain reaction has proved to be a sensitive and specific method for the detection of contaminating tumour cells in peripheral blood. The aim of this study was to report the early clinical observations made using this technology in neuroblastoma patient blood samples.

Calcium requirement--a reappraisal of the methods used in its determination and their application to patients with osteoporosis.

The accepted practice of calculating the dietary calcium requirement from the relationship between calcium balance and intake was recently criticized on mathematical grounds. To try to determine the appropriate calcium intake in patients with osteoporosis, I examined the relationships between calcium intake, output, and balance in a group of such patients. Calcium-balance studies were performed on 25 patients with untreated osteoporosis: intake (x +/- SEM) was 30.