The PEX gene: not a simple answer for X-linked hypophosphataemic rickets and oncogenic osteomalacia.
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Biomedical subjects
Publications and source records attributed to A E Nelson.
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Oncogenic osteomalacia is a syndrome associated with rare, usually mesenchymal tumours, which is characterized by hypophosphataemia, phosphaturia and low concentrations of 1,25-dihydroxyvitamin D. The reversal of clinical and biochemical abnormalities following removal of the tumour, indicates it is the source of a humoral factor that is responsible for these abnormalities. It has been demonstrated that the humoral factor inhibits renal phosphate uptake and reduces 1,25-dihydroxyvitamin D production. Although there is evidence that it may act via parathyroid hormone/parathyroid hormone-related peptide receptors and may be a peptide, the factor has not yet been identified, nor has its relationship to factors involved in X-linked hypophosphataemic rickets been established. We propose unifying hypotheses for the pathogenesis of oncogenic osteomalacia and X-linked hypophosphataemic rickets which involve defects in the PEX gene. These hypotheses do not fully explain all the available data and it remains possible that hormone(s) with little or no role in X-linked hypophosphataemic rickets may be responsible for oncogenic osteomalacia.
A hematopoietic stem cell transplantation (HSCT) is used as a treatment for cancer or nonmalignant hematological disorders in children. Little information is known about how an HSCT affects the mothers of these patients. The purposes of this repeated measures study were to examine the stress responses of mothers at four times during their child's hospitalization for an HSCT and to determine the relationships among mothers' stress responses and the resources for coping and social support. Maternal anxiety mean scores decreased significantly over time although a majority of the mothers had moderately high anxiety scores at all times. Mean scores of mothers' depressive symptomatologies decreased significantly over time. A majority of the mothers had depressive symptomatology scores above the cut-off score that indicates being at-risk for developing depression. At each of four data collection times, a specific coping style (defined as active reviewing of feelings or information associated with the situation) significantly explained the variance in mothers' scores for anxiety, depressive symptomatology, somatic complaints, and sleep behavior. Social support significantly explained differences in depressive symptomatology scores only at data collection times 1 and 3. Health care providers need to assess mothers for stress responses and assist them in dealing with their feelings and in understanding the information associated with an HSCT.
Oncogenic osteomalacia is a condition where renal phosphate wasting occurs causing defective mineralisation, in the presence of a tumor. Cultures of cells were established from a hemangiopericytoma resected from a patient with oncogenic osteomalacia. Conditioned media from the cells inhibited phosphate uptake in opossum kidney cells and stimulated of cAMP in rat osteosarcoma cells, a standard parathyroid hormone (PTH)-like assay. This cAMP stimulation was suppressed by the PTH analogue, 3-34 bPTH and also by heat and trypsin treatment of the media. Tests of conditioned media for PTH and parathyroid hormone related protein (PTHrP) immunoreactivity were negative, however, and no hybridisation to probes for PTH, PTHrP or human stanniocalcin was detected in tumor cell RNA on Northern blot. These data support the hypothesis that tumors responsible for oncogenic osteomalacia produce a humoral substance that reduces renal phosphate reabsorption and provide evidence that the factor may act via PTH/PTHrP receptors.
One thousand one hundred eighty men in a medical outpatient clinic were screened as to the presence of impotence. Four hundred one men (34%) were impotent, and of those, 188 (47%) chose to be examined for their problem. After a comprehensive evaluation the following diagnoses were obtained: medication effect, 25%; psychogenic, 14%; neurological, 7%; urologic, 6%; primary hypogonadism, 10%; secondary hypogonadism, 9%; diabetes mellitus, 9%; hypothyroidism, 5%; hyperthyroidism, 1%; hyperprolactinemia, 4%; miscellaneous, 4%; and unknown causes, 7%. The mean age of the impotent patients was 59.4 years, and the prevalence of alcoholism was 7%. Luteinizing hormone, follicle-stimulating hormone, testosterone, thyroxine, triiodothyronine (T3), T3 resin uptake, and prolactin studies were necessary to diagnose individual cases. We conclude that erectile dysfunction is a common and often overlooked problem in middle-aged men followed in a medical clinic.
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The effect of biofeedback during brief periods of relaxation was examined. Two groups (10 subjects in each group) were asked to relax as completely as possible during a series of six 3-minute relaxation periods in each of two 1-hr sessions. One group received biofeedback based on finger pulse volume (FPV) during the relaxation trials, while the other group received no biofeedback. Measures of heart rate, respiration rate, skin conductance level, and FPV were recorded during the sessions, and subjective ratings concerning relaxation were obtained after each session. The results showed that FPV scores for the groups differed during the relaxation trials of the second session, but other measures failed to distinguish between the groups. The group that received FPV feedback revealed a significantly higher level of FPV (relative to baseline) than the group that received no feedback.
A sensitive and specific radioimmunoassay for plasma arginine vasopressin (AVP) has been used to study the effects of blood osmolality and volume in regulating AVP secretion in unanesthetized rats. Under basal conditions, plasma AVP and osmolality were relatively constant, averaging 2.3+/-0.9 (SD) pg/ml and 294+/-1.4 mosmol/kg, respectively. Fluid restriction, which increased osmolality and decreased volume, resulted in a progressive rise in plasma AVP to about 10 times basal levels after 96 h. A 2-3-fold increase in plasma AVP occurred as early as 12 h, when osmolality and volume had each changed by less than 2%. Intraperitoneal injections of hypertonic saline, which had no effect on blood volume, also produced a rise in plasma AVP that was linearly correlated with the rise in osmolality (r > 0.9) and quantitatively similar to that found during fluid restriction (plasma AVP increased 2-4-fold with each 1% increase in osmolality). Intraperitoneal injection of polyethylene glycol, which decreased blood volume without altering osmolality, also increased plasma AVP but this response followed an exponential pattern and did not become significant until volume had decreased by 8% or more. At these levels of hypovolemia, the osmoregulatory system continued to function but showed a lower threshold and increase sensitivity to osmotic stimulation. We conclude that AVP secretion is regulated principally by blood osmolality but that the responsiveness of this mechanism may be significantly altered by modest changes in blood volume.
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