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Few studies have comprehensively examined the profile of cognitive functioning in first episode psychosis patients throughout the lifespan, and from first episode to chronic stage. We assessed functioning in general and specific cognitive functions, comparing both schizophrenia (N = 64) and bipolar I (N = 19) patients to controls (N = 103). Participants were from a population-based, case-control study of first episode psychosis patients, who were followed prospectively up to 10 years post first admission. A cognitive battery was administered at baseline and follow-up. By combining longitudinal and cross-sectional data, we were able to examine the cognitive profile of patients and controls throughout the entire age range of our sample (16-65). Schizophrenia patients exhibited widespread declines in IQ, executive function, visual memory, language ability, and verbal knowledge. However, the ages at which these declines occurred differed between functions. Deficits in verbal memory, working memory, processing speed, and visuospatial ability, on the other hand, were present at the first episode, and remained relatively static thereafter. Bipolar I patients also showed declines in IQ, verbal knowledge, and language ability, albeit at different ages to schizophrenia patients and only in verbal functions. Deficits on measures of verbal memory, processing speed, and executive function remained relatively static. Thus, both schizophrenia and bipolar I patients experienced cognitive decline in general and specific functions after the first episode, but the age at which these declines occurred differed between disorder and function. Cognitive remediation efforts may be most fruitful when targeting individual functions during specific time periods throughout adulthood., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Circulating levels of parathyroid hormone (PTH) in six patients with pseudohypoparathyroidism type I (PSPI) have been measured by two immunoassays and by cytochemical bioassay and compared with measurements in normal subjects and patients with clinically defined hyper- and hypoparathyroidism. In all PSPI patients, the levels of immunoreactive PTH were in the hyperparathyroid range, whereas the bioactive levels were either in the normal or close to the normal range. In one patient from whom the dihydrotachysterol therapy was withdrawn, both immunoreactive and bioactive PTH concentrations increased. The finding that the PTH measured by RIA in these PSPI patients may have reduced biological activity may explain some of the clinical findings of hypoparathyroidism in this syndrome.

During a 15-month period, 47 elderly female patients admitted to hospital with a fractured neck of femur were studied immediately prior to discharge, in comparison with 34 elderly female control patients undergoing elective surgery who had been admitted over the same period to the same orthopaedic wards. The principal differences between the two populations were that the fracture patients had a lower forearm trabecular bone density, with lower bodyweight (both lower muscle mass and lower fat content), increased body sway, worse eyesight and reduced mental acuity. The serum biochemistry of the two groups was almost indistinguishable except that the fracture patients tended to have slightly lower concentrations of proteins. There was no evidence to implicate dietary vitamin D deficiency, osteomalacia, oestrogen deficiency or alcoholism in the aetiology of the fracture, nor was there evidence to suggest alterations in endocrine function with respect to cacitonin or parathyroid hormone.

The adult greyhound was found to be similar to adult man with respect to kinetic and histomorphometric indices of calcium metabolism. The relationship between trabecular bone tissue balance and the pattern of human PTH fragment 1-34 (hPTH 1-34) administration by daily injections or continuous sc infusions was investigated in this model and the results compared to those from a clinical trial of hPTH 1-34 in involutional osteoporosis (peptide administration by single daily injections). In the dogs, the daily injection regime elevated plasma levels of immunoreactive hPTH 1-34 for no more than 4 h/day. The greyhounds so treated showed significantly increased indices of bone formation (surface osteoid, plasma alkaline phosphatase activity, and skeletal accretion rate of calcium) and resorption (number of osteoclasts, resorption surfaces). Iliac trabecular bone volume increased significantly, as it did in the patients. The infusions did not significantly increase the trabecular bone volume or the 47Ca accretion rate, two parameters which increased in parallel in dogs and patients treated successfully by daily injections. The osteoclastic surfaces, however, were clearly increased by continuous infusions, while the increases in the osteoblastic surfaces were less statistically significant. Since hPTH 1-34 may inhibit osteogenesis in Friedenstein chambers, it is possible that the increased osteoblastic activity induced by the daily injection regime in trabecular bone is dependent on the noncontinuous nature of the PTH stimulus.

An international collaborative study of an ampouled preparation of highly purified human PTH (hPTH) was carried out on behalf of WHO by 29 laboratories in 12 countries. The results reported here show that the preparation of human PTH, freeze-dried and sealed in ampoules coded 79/500, has appropriate biological activities in in vitro bioassay systems, is free from cleaved products, as shown by high performance liquid chromatography, and is stable under conditions of accelerated thermal degradation. The ampouled hPTH was calibrated by immunoassays against the Research Standard of hPTH for immunoassay (ampoule code 75/549) distributed internationally from the National Institute for Biological Standards and Control since 1977. On the basis of this study and the agreement of the participants, the preparation coded 79/500 was established in 1981 by WHO as the First International Reference Preparation of PTH, Human, for Immunoassay; the unitage was defined as 0.1 IU (100 mIU)/ampoule. An ampouled preparation of unpurified extracted hPTH had characteristics similar to those of the purified ampouled preparation and was calibrated simultaneously to serve as a research reagent for immunoassay. Two ampouled lyophilized materials derived from tissue culture medium and secondary hyperparathyroid plasma, representative of biological fluids widely used as working standards for clinical immunoassays, were included in the collaborative study for comparative purposes. Results from immunoassay, bioassay, and high performance liquid chromatography systems suggest that these preparations contained little intact hPTH and consisted of mixtures of metabolites having predominantly carboxyl region immunoreactivity.

Daily injections of low doses of a synthetic fragment of human PTH [hPTH-(1-34) have increased iliac trabecular bone volume when used in the treatment of osteoporosis. In approximately 50 patients no major side-effects had occurred. However, during daily sc 100-micrograms injections of the peptide, one patient repeatedly developed parathyroid hypofunction which resolved each time treatment was stopped. Specific immunoglobulin G (IgG) antibodies binding [125I]hPTH-(1-34) were identified in the patient's serum, and positive immunohistochemical reactions were obtained when bovine parathyroid sections were exposed to the patient's IgG. After adsorption with PTH, the patient's IgG, free of anti-PTH antibodies, reacted with renal cell membranes, as demonstrated by indirect immunofluorescence and blocked renal PTH-dependent adenylate-cyclase activation in vitro. These results support the hypothesis that anti-PTH receptor as well as anti-PTH antibodies were generated during hPTH-(1-34) treatment, which led to the development of hypoparathyroidism when their titers were high.

Several studies have revealed a variety of interactions between PTH and ACTH. The existence of a significant area of homology in the bioactive regions of the two molecules has been proposed as a possible reason for such interactions. To clarify the relationship, corticosteroidogenic and cAMP accumulative effects of bovine PTH (bPTH 1-84), its amino-terminal fragment (bPTH 1-34), and the amino terminal fragment of human PTH (hPTH 1-34) were compared with ACTH 1-39 by determining their dose-response characteristics in collagenase-dissociated adrenocortical cells from rats. bPTH 1-84 and bPTH 1-34 (10(-8)-10(-5)M) did not alter steroid production of the cells nor did 10(-6)M bPTH 1-34 affect the steroid response curve to ACTH 1-39. However, the degree of steroidogenesis elicited by hPTH 1-34 over the dose range 3.3 X 10(-7)-3.3 X 10(-5)M was the same as that elicited by ACTH 1-39 over the range 10(-11)-10(-9) M. cAMP generation with hPTH 1-34 was maximal at 10(-4) M but the correlation between the steroid and cAMP responses with ACTH 1-39 was noticeably different from that with hPTH 1-34. In experiments with ACTH 6-24 (a competitive inhibitor of ACTH 1-39), both steroid and cAMP responses to hPTH 1-34 were greatly reduced. Oxidized hPTH 1-34 did not elicit any steroid production nor did several other peptide hormones (arginine vasopressin, angiotensin II, calcitonin, insulin, GH) at 10(-5) M. These observations indicate that hPTH 1-34 can exert a direct and specific effect on rat adrenocortical cells revealing the peptide as a full agonist for steroid production in this system. We suggest that it is a combination of sequence homology and conformational structure which permits hPTH 1-34 to interact with, and elicit its response through, the receptor for ACTH 1-39.

Synthetic 1-84 human PTH (hPTH) peptides (with either asparagine) or aspartic acid at position 76) were compared with natural bovine PTH (bPTH) in three in vivo bioassays. Surprisingly, in the chick hypercalcemia bioassay, the human 1-84 peptides were approximately 3 times more potent on a molar basis than bPTH. In contrast, in an in vivo mouse kidney cAMP accumulation bioassay, these human peptides were 3-6 times less potent than bPTH. This low potency of synthetic hPTH relative to bPTH in the renal cAMP assay is in accordance with published relative potency estimates for natural extracted hPTH in in vitro rat renal membrane adenylate cyclase assays. The human and bovine 1-84 peptides were weakly active in an in vivo mouse calvaria cAMP accumulation system, producing a shallow dose-response curve which was not suitable for any quantitative estimates of potency. In contrast, both human and bovine 1-34 fragments were highly active in stimulating accumulation of cAMP in calvaria thus emphasizing the qualitative differences between 1-84 PTH and the 1-34 fragment of both species of PTH. Despite the homology between human and bovine 1-84 PTH, they have markedly different quantitative biological effects on hypercalcemia in chicks and in vivo renal cAMP accumulation in mice. Any estimate of the biological potency of human 1-84 PTH, relative to bovine 1-84 PTH, will need to be defined in terms of the nature and species of the biological test system.