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Biomedical subjects

K J Martin

Publications and source records attributed to K J Martin.

At least 55 records · Page 3Linked to original sources
PubMed1995

Workers' compensation: case management strategies.

1. Comprehensive workers' compensation case management involves goals at all levels of prevention. The goal for primary prevention is decreasing the risk of job injury; for secondary prevention, preparing for early intervention in injury events; and for tertiary prevention, assisting injured employees to regain maximum health. 2. The major roles of the occupational health nurse in implementing a case management program are: assessing workplace safety and health, establishing treatment networks, assisting employees with choices from among treatment options, and creating a continuous communication feedback loop among all parties involved. 3. Case management systems may be evaluated from four perspectives: consumer satisfaction, process, outcome, and cost effectiveness. A combination of the four methods will yield a strong indication of program value and highlight areas in need of improvement.

Humans↗
PubMed1994

Cell cycle studies of cyclocreatine, a new anticancer agent.

Cyclocreatine (CCr), a substrate analogue of creatine kinase (CK), exhibits antitumor activity in vitro and in vivo. To address its mechanism of action, we have examined its effects on tumor cell proliferation, viability, and cell cycle progression. Complete inhibition of proliferation of ME-180 cervical carcinoma cells was observed within 8 h of exposure to CCr and was characterized by an inhibition of progression out of all phases of the cell cycle. This initial effect was partially reversible on drug removal. Increased cytotoxicity was observed after several days of drug exposure and was most specific to cells in S. Previous studies have shown that CCr supports ATP regeneration through the CK system less efficiently than the natural substrate creatine and that CCr is active against tumor cell lines with elevated levels of CK. We propose here that the general inhibition of cell cycle progression reflects an effect of CCr on tumor cell energy availability through CK and that impaired energy homeostasis for several days leads to tumor cell death. Our results point out the unique nature of CCr as an anticancer agent that inhibits progression out of all phases of the cell cycle.

Antineoplastic Agents↗
PubMed1994

Evaluation of creatine analogues as a new class of anticancer agents using freshly explanted human tumor cells.

BACKGROUND: The creatine kinase (CK) isozymes and their substrates, creatine and creatine phosphate, are believed to play a pivotal role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, and brain. This enzyme system may also be involved in the process of cellular transformation. Inhibition of tumor cell growth by creatine analogues has been observed and may be due to the ability of these analogues to impair cellular energy generation and utilization. PURPOSE: An in vitro human tumor colony-forming assay was used to predict the clinical usefulness of creatine analogues as anticancer agents. METHODS: The ability of cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) and homocyclocreatine (1-carboxyethyl-2-iminoimidazolidine) to inhibit the growth of cells prepared from tumor samples taken directly from patients was evaluated by quantitative measurement of colony formation in a soft-agar cell culture assay system. Cyclocreatine was tested in this human tumor colony-forming assay at concentrations ranging from 0.067 to 20 mM against 128 tumor samples, 51 of which formed colonies in the assay and were considered evaluable. Homocyclocreatine was similarly tested at concentrations from 0.2 to 20 mM against 139 tumor samples; 54 were considered evaluable. The colony-forming assay was also used to compare the efficacy of the creatine analogues to representatives from the six major classes of standard chemotherapeutics (alkylating agents, antimetabolites, DNA intercalators, platinum compounds, topoisomerase inhibitors, and tubulin-interacting agents). In addition, CK levels were measured in 192 tumor samples that were taken from 166 patients. RESULTS: Cyclocreatine and homocyclocreatine, at concentrations previously achieved in animal tissues (7-20 mM), had antitumor activity against 19% and 50%, respectively, of tumor samples that formed colonies in the assay. Cyclocreatine was effective against a subset of tumors sensitive to homocyclocreatine (P = .023; Fisher's exact test), which was the more potent creatine analogue in this assay (P < .001; McNemar's test). No relationships were seen between tumor samples sensitive to the creatine analogues and those sensitive to standard chemotherapeutics. Pairwise Wilcoxon rank sum tests indicated that CK activity was significantly higher in tumors with any growth in the colony assay compared with tumors that did not grow (P < .025). CONCLUSIONS: The creatine analogues, cyclocreatine and homocyclocreatine, effectively reduced colony formation of freshly explanted human tumor cells. The mechanism of action or resistance to these compounds seems to differ from those of standard chemotherapeutics. IMPLICATIONS: Creatine analogues that may alter the energy status of the tumor cell potentially represent promising new anticancer agents that function through a unique mechanism.

Antineoplastic Agents↗
PubMed1994

Effect of U-73,122, an inhibitor of phospholipase C, on actions of parathyroid hormone in opossum kidney cells.

The relative roles of the adenylate cyclase-protein kinase A system (AC-PKA), the phospholipase C-protein kinase C system (PLC-PKC), and increases in cytosolic calcium in mediating the final actions of parathyroid hormone (PTH) remain ill defined. Although an important role for the PLC-PKC system in the regulation of phosphate transport in response to PTH has been suggested, previous studies from our laboratory and others, in OK cells, have emphasized the major role of AC-PKA. The present studies were designed to dissociate the second messengers for PTH by using an inhibitor of PLC (U-73,122). Studies were performed in confluent cultures of OK cells with and without preincubation with U-73,122 (1 microM). This inhibitor did not alter adenosine 3',5'-cyclic monophosphate (cAMP) production or the activation of PKA in response to PTH. Preincubation with U-73,122, however, totally abolished PTH-stimulated increases in diglyceride mass, consistent with inhibition of PLC. Activation of particulate PKC was then examined in response to PTH in the absence and presence of U-73,122. Although PTH resulted in an increase in particulate PKC activity in control cultures, this effect was abolished in the presence of U-73,122 and actually decreased significantly. Therefore, having documented marked attenuation of PLC-PKC, we next examined the effects of PTH on phosphate transport. Basal phosphate uptake was not altered by 1 microM U-73,122. Dose-response curves of the inhibition of phosphate transport in response to PTH were identical in the presence or absence of U-73,122. Thus inhibition of PLC and PKC activities did not alter the effects of PTH on phosphate transport.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1994

Effect of triamcinolone on parathyroid hormone-stimulated second messenger systems and phosphate transport in opossum kidney cells.

Although PTH is known to stimulate both the adenylate cyclase/protein kinase-A system and the phospholipase-C/protein kinase-C second messenger systems, the relative roles of these second messenger pathways remain unclear. The present studies were designed to examine the effect of triamcinolone on PTH-stimulated second messenger systems and phosphate transport in confluent cultures of opossum kidney cells. Triamcinolone was added to these cultures at a concentration of 10 nM for 24-48 h. Neither cell number nor protein content was changed by this treatment. The addition of triamcinolone did not alter PTH receptor binding or competitive displacement radioligand binding assay curves. PTH-stimulated cAMP generation and activation of protein kinase-A were not altered by triamcinolone. The glucocorticoid, however, increased basal phosphate uptake from 1.0 +/- 0.1 to 1.28 +/- 0.1 pmol/5 min.culture (P < 0.01). Phosphate transport was significantly decreased by PTH (0.01 nM) in the triamcinolone-treated cultures, but not in control cultures. Phosphate uptake in the presence of maximal doses of PTH was similar in both control and triamcinolone-treated cultures. Thus, the PTH-responsive component of phosphate transport was preserved, and the threshold dose for the effect of PTH was reduced after treatment with triamcinolone. Studies were then performed to evaluate the alternate second messenger pathway. In control cultures, PTH rapidly increased the level of diglyceride mass, as measured by diglyceride kinase assay, from 0.18 +/- 0.01 to a peak of 0.26 +/- 0.02 mol/100 mol total phospholipid (P < 0.002), 1 min after addition of the hormone. Triamcinolone pretreatment for 48 h, however, elevated the basal diglyceride levels, but the increase after the addition of PTH was totally abolished. The absence of an increase in diglyceride upon stimulation with PTH correlated with elimination of the PTH-stimulated increase in the activity of particulate protein kinase-C. Thus, in triamcinolone-treated cells, the effect of PTH on phosphate transport was preserved, and the threshold dose of PTH-induced alteration in phosphate transport was reduced in the absence of stimulation of this alternate second messenger pathway. These data show that triamcinolone in opossum kidney cells does not alter PTH activation of the cAMP/protein kinase-A system, but eliminates the increase in diglyceride and the activation of protein kinase-C in response to PTH. These studies emphasize the major role of the protein kinase-A system in the regulation of phosphate transport by PTH.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Parathyroid hormone increases the expression of receptors for epidermal growth factor in UMR 106-01 cells.

PTH administration in vivo increases osteoblast number and activity, resulting in increased bone formation, and also increases osteoclast-mediated bone resorption. Studies in vitro, however, have shown that the actions of PTH on osteoblast-like cells are inhibitory and catabolic, as shown by decreases in growth rate and collagen synthesis and increases in collagenase production. The present studies were designed to investigate possible mechanisms for these observations by examining the effects of PTH on the response of osteoblast-like cells to the osteoblast growth factor, epidermal growth factor (EGF). Confluent cultures of UMR 106-01 cells were treated with rat PTH-(1-34) for periods up to 72 h, and EGF receptors were measured with [125I]EGF. PTH, in a dose- and time-dependent manner, increased the number of EGF receptors 2-fold. The half-maximal effect of PTH occurred at a concentration of 1 nM, the same PTH concentration that resulted in half-maximal increases in cAMP generation. The increase in EGF binding was associated with an enhanced biological effect, as shown by augmentation of EGF-stimulated diglyceride production. The effect of PTH could be reproduced by the addition of 8-bromo-cAMP, but not by the phorbol ester phorbol myristate acetate. In the presence of cyclohexamide, the effect of PTH on EGF binding was abolished, suggesting that new protein synthesis was required to increase the number of EGF receptors. Northern blots of total RNA, using a cDNA probe encoding the extracellular domain of the rat EGF receptor, revealed that PTH treatment resulted in a 2- to 3-fold increase in the level of EGF receptor mRNA. These data suggest that the proliferative effects of PTH on the osteoblast may be mediated indirectly by a PTH-induced increase in the number of EGF receptors.

Animals↗
PubMed1994

Neurotensin binding to human embryonic lung fibroblasts.

Several neuropeptides have been shown to regulate the function of cells involved in immune response and inflammation. Neurotensin is a 13 amino acid neuropeptide localized primarily to the nervous system and gut. Neurotensin also stimulates mast cell degranulation and enhances phagocytic and cytolytic capability of macrophages, suggesting that this peptide regulates inflammatory and immune responses. Fibroblasts play an important role in inflammation and tissue healing, and these processes may be regulated by several neuropeptides that have been shown to bind to fibroblasts. However neurotensin receptors have not been identified on fibroblasts. Human embryonic lung fibroblasts (HELF) were examined for binding and biological effects of neurotensin. 125I-neurotensin binding to adherent and confluent human embryonic lung fibroblasts (HELF), plated in 12mm diameter wells was specific and saturable. Computer-assisted resolution of the binding data demonstrated two classes of binding sites: a high affinity, low capacity site (Kd = 1.6 x 10(-11) M, 19.5 x 10(7) sites/well), and a low- affinity, high-capacity site (Kd = 10(-8) M, 4 x 10(9) sites/well). Neurotensin stimulated immediate, transient, dose-dependent increases of cytosolic calcium in HELF (threshold dose: 10(-11) M), suggesting release of calcium from intracellular stores. The novel finding of neurotensin receptors on fibroblasts provides further support for this neuropeptide's role as a regulator of inflammatory and immune responses.

Calcium↗
PubMed1993

Corporate perspective of the role of the occupational health nurse.

One hundred and twenty-three Ohio employers were surveyed about expectations for occupational health nurse performance of 20 current and desired future activities. Employers identified activities that (a) the nurse was currently performing, or (b) would be desired in the future, or (c) were not appropriate for the nurse. Findings showed occupational health nurses are counseling employees, treating illness and injury, evaluating safe return to work, and tracking workers' compensation cases. Activities most desired in the future are analyses of trends in health programs and study of cost-effective health program alternatives. Activities most frequently selected require skills of evaluation, budgeting, and cost-benefit analysis. Most occupational health nurses have not had the opportunity to learn skills of fiscal management; therefore meeting employer expectations will require new education.

Administrative Personnel↗
PubMed1993

Desensitization of calcium messenger system in parathyroid hormone-stimulated opossum kidney cells.

We have studied the desensitization of the calcium message system to parathyroid hormone (PTH) by monitoring intracellular calcium concentration ([Ca2+]i) in an opossum kidney cell line (OKP). PTH (10(-7) M) caused a transient increase in [Ca2+]i, with an average peak height of 48.7 +/- 4.7% above baseline (n = 32). Cells stimulated with either 10(-7) or 10(-8) M PTH did not respond to a second challenge with a maximal dose (10(-7) M) of the hormone, whereas lower concentrations of PTH (10(-9) M and 10(-10) M) only partially desensitized the cells, since a [Ca2+]i transient of smaller amplitude (12.7 +/- 2.1 and 40.6 +/- 6.2% above baseline, respectively) was observed with a second stimulation. Desensitization developed within 5 min of initial hormone exposure, when PTH receptor binding was not significantly decreased. Maximal reduction of PTH binding sites (37.0 +/- 1.4%) was achieved only after 2 h. Partial desensitization was reproduced by 10(-9) M phorbol 12-myristate 13-acetate (PMA) but not by dibutyryladenosine 3',5'-cyclic monophosphate, and it was blocked by staurosporine. However, staurosporine had no effect on the complete desensitization induced by high doses of PTH. At 10(-9) M, PTH also caused a time-dependent desensitization of the adenosine 3',5'-cyclic monophosphate (cAMP) response, with maximal inhibition achieved after 2 h. PMA also decreased the cAMP response to PTH, but its inhibitory effect was less potent than that of 10(-9) M PTH. Therefore PTH induces a dose-dependent homologous desensitization of the Ca2+ message system in OKP cells, independent of receptor occupancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1993

Being off work, preparing to return to work: how client-nurse interactions can affect employee well being.

1. Three central themes emerged through exploration of the meaning of being off work, preparing to return to work: changing expectations, obstacles being overcome, and gaining control of one's life. 2. Preparing to return to work is a positive shift in expectations as the inabilities and obstacles are overcome in the process of regaining self. 3. The occupational health nurse should focus attention on understanding the perceived need for control and the perceived need for being productive. 4. The occupational health nurse can provide information, serve as a resource, act as a liaison among members of the health care team, and explore alternate duty options for the recovering employee.

Absenteeism↗
PubMed1992

A new sensitive homologous radioimmunoassay for amino-terminal parathyroid hormone in the rat.

The determination of circulating biologically active PTH in the rat has been difficult due at least in part to the inability to develop an antibody suitable for RIA of rat PTH. However, since the amino acid sequence of the rat PTH molecule has been deduced by molecular techniques, corresponding synthetic peptides have made it possible to produce such an antibody. A total of 12 roosters were immunized with synthetic rat PTH-(1-34), and one animal, RD1, developed a sensitive antibody against this amino-terminal region of the rat PTH molecule. To further increase the sensitivity of the RIA, we utilized an analog of rat PTH, Tyr1 rat PTH-(2-34), as the radioligand, which can be iodinated to high specific activity (450 microCi/micrograms). The iodinated peptide was purified by HPLC using a C18 Nova Pak HPLC column and a 20-60% acetonitrile gradient in 0.1% TFA. Synthetic rat PTH-(1-34) was used as the standard. To validate the RIA, we measured PTH under a variety of metabolic conditions. Normal values for PTH were 55.6 +/- 3.9 pg/ml (n = 26). Levels in parathyroidectomized (PTX) rats (n = 9) were undetectable, but renal insufficiency and vitamin D deficiency increased PTH to 587.4 +/- 141.3 pg/ml (n = 73) and 1662.0 +/- 137.8 (n = 27), respectively. Intraperitoneal (IP) administration of ethylenediaminetetraacetic acid (EDTA), 200 mg/kg, was used to decrease ionized calcium (ICa) from 4.75 +/- 0.07 to 3.55 +/- 0.10 mg/dl, which increased PTH from 51.3 +/- 5.9 to 109.3 +/- 13.4 pg/ml (n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Pulse oral calcitriol for the treatment of hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis: preliminary observations.

A direct effect of calcitriol on the regulation of the secretion of parathyroid hormone (PTH) has been shown in vitro and in vivo. In patients with renal failure on maintenance hemodialysis, it has been shown that intravenous (IV) administration of calcitriol appears to be superior to continuous oral administration. This may be due to the higher levels of calcitriol obtained in blood with consequent improved delivery of calcitriol to peripheral target tissues including the parathyroid glands. However, IV administration of calcitriol, is not practical for patients with end-stage renal disease (ESRD) who are maintained on continuous ambulatory peritoneal dialysis (CAPD). The present studies were designed to investigate whether intermittent administration of large doses of calcitriol orally ("pulse therapy") could mimic the effects of IV calcitriol in hemodialysis patients and achieve suppression of PTH secretion. Studies were performed in five patients who had been maintained on CAPD for more than 6 months. After basal determinations of calcium, phosphorus, and PTH, therapy was begun with calcitriol administered orally in a dose of 5 micrograms given twice per week. Calcium carbonate was continued as a phosphate binder. Dialysate calcium concentration was 1.75 mmol/L (3.5 mEq/L). With this therapy, PTH levels decreased rapidly, and, after 4 to 6 weeks of therapy, reached values 60% lower than pretreatment values. Mean values for serum calcium did not change significantly (2.29 +/- 0.12 mmol/L [9.6 +/- 0.5 mg/dL] before treatment compared with 2.32 +/- 0.08 mmol/L [9.7 +/- 0.25 mg/dL] after therapy). Mean serum phosphorus was also unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

The role of protein kinase-A activity in the evaluation of agonist/antagonist properties of analogs of parathyroid hormone-related protein in opossum kidney cells.

Structural modifications of the amino-terminal region of PTH resulted in the generation of PTH analogs with potent antagonist activities and markedly reduced agonist activities. Further development of these structure-function relationships to modifications of the sequence of the PTH-related protein (PTHrP) resulted in PTH/PTHrP antagonist analogs with increased antagonist activity and little if any agonist effects. Since studies from our laboratory have shown that measurement of protein kinase-A activity appears to be a more sensitive index of the actions of PTH than measurements of total cAMP, the present studies were designed to examine the effects of a series of PTHrP-based peptides for agonist/antagonist effects in opossum kidney (OK) cells. The results show that PTHrP-(7-34)NH2, which does not increase cAMP, displays agonist activity in terms of increasing protein kinase-A activity. Furthermore, [Leu11,D-Trp12]PTHrP-(7-34)NH2 and [D-Trp12]PTHrP-(7-34)NH2, which appear to be effective antagonists of rat PTH-(1-34)-stimulated cAMP generation, were less effective in antagonizing the effects on protein kinase-A and only [Leu11,D-Trp12] PTHrP-(7-34)NH2 appeared to exhibit any antagonist activity. The Ki for [Leu11,D-Trp1/]PTHrP-(7-34)NH2 to antagonize the stimulatory effect of 1 nM rat PTH-(1-34) was easily demonstrable by measurements of cAMP, but could not be demonstrated using the assay of protein kinase-A activity. These data underscore the observation that measurement of protein kinase-A is a more sensitive index of the effects of PTH than measurements of cAMP and that significant agonist activity on the cAMP/protein kinase pathway cannot be excluded without measurements of protein kinase-A activity.

Animals↗
PubMed1992

Biologic activities of parathyroid hormone (1-34) and parathyroid hormone-related peptide (1-34) in isolated perfused rat femur.

Parathyroid hormone-related peptide (PTHrP) has substantial homology with both human and rat parathyroid hormone (66% and 73%, respectively) in the first 15 amino acids. PTHrP (1-34) stimulates cyclic adenosine monophosphate (cAMP) release in bone and kidney, and these effects are felt to occur through interaction with the parathyroid hormone (PTH) receptor. Differences in the biologic potency between rat PTH(1-34) and human PTH(1-34)--and between PTHrP and PTH--have been described in a variety of experimental systems. In this study, we compared the bioactivity of these three amino-terminal synthetic fragments on the stimulation of cAMP formation in an isolated perfused rat femur preparation. Dose-response experiments demonstrated that PTHrP(1-34) was more potent in stimulating cAMP release than human PTH(1-34), whereas PTHrP(1-34) and rat PTH(1-34) were equipotent. Despite the fact that the extraction of immunoreactive rat PTH(1-34) and human PTH(1-34) was the same, rat PTH(1-34) was more potent in stimulating adenylate cyclase activity than human PTH(1-34). These data show that the isolated perfused rat femur preparation is an effective method for evaluation of the effects of PTH and PTHrP. Despite significant structural differences in the binding domain between rat PTH(1-34) and PTHrP(1-34), the effects of rat PTH(1-34) and PTHrP(1-34) are similar. Because the structure of rat PTHrP(1-34) and human PTHrP(1-34) are identical, and because it is desirable to utilize homologous systems to study the potency and effects of test peptides, it would appear that rat PTH(1-34) is the most appropriate peptide for comparison with PTHrP in rat-based experimental systems.

Amino Acid Sequence↗
PubMed1992

Failure of CAPD patients to respond to an oral iron absorption test.

CAPD patients require supplemental iron to maintain a response to erythropoietin. Because of limited availability of parenteral iron dextran, oral iron must be used. However, oral iron may not be effective in most dialysis patients. To determine if oral iron is well absorbed, a modified oral iron absorption or tolerance test was performed in CAPD patients using two oral iron preparations. Serum irons were measured at baseline in a fasting state and repeated two hours after the ingestion of 325 mgs ferrous sulfate in five CAPD patients. In addition, eight patients had serum irons determined before and two hours after taking liquid oral ferrous fumarate in capsule form. Healthy controls were compared with each group. All five patients who received ferrous sulfate had borderline to low normal serum iron and iron stores. Average increase in serum irons was only 19 mcg/dl in patients compared to 52 mcg/dl in controls. Patients receiving ferrous fumarate rose only 14 mcg/dl compared to 60 mcg/dl in controls. We conclude that oral iron is poorly absorbed in most CAPD patients and that the oral iron absorption test may be helpful in identifying patients who are effective iron absorbers. Unfortunately, until parenteral iron dextran is readily available, oral iron therapy is the only alternative for iron supplement. The oral iron absorption test may predict who will respond to oral iron in the long-term.

Administration, Oral↗
PubMed1992

Stress related workers' compensation claims: recommendations involving records release.

1. The cost of stress claims is predicted to cripple the workers' compensation system, where stress claims are burgeoning and the average payout is twice that of a typical injury. The major reason to release medical records in a stress claim is to determine the validity of the claim arising from the job. 2. Occupational health nurses are frequently asked by the courts to reveal personal client information and may not be protected by the "nurse-client relationship" or "privileged communication." Politically, very little interest has been shown in restricting disclosure of private information. 3. Both ANA and AAOHN have adopted strong positions about safeguarding privacy. Legally, the ultimate responsibility for wrongful acts committed by the nurse falls on the individual nurse. 4. The most important reason to guard confidential health information is the basic tenet of the nurse-client relationship in which personal matters are held in confidence. To break this trust is to jeopardize the ability to provide optimal client care, which is the essence of nursing.

Confidentiality↗
PubMed1992

Machine safety: proper safeguarding techniques.

1. OSHA mandates certain safeguarding of machinery to prevent accidents and protect machine operators. OSHA specifies moving parts that must be guarded and sets criteria for the guards. 2. A 1989 OSHA standard for lockout/tagout requires locking the energy source during maintenance, periodically inspecting for power transmission, and training maintenance workers. 3. In an amputation emergency, first aid for cardiopulmonary resuscitation, shock, and bleeding are the first considerations. The amputated part should be wrapped in moist gauze, placed in a sealed plastic bag, and placed in a container of 50% water and 50% ice for transport. 4. The role of the occupational health nurse in machine safety is to conduct worksite analyses to identify proper safeguarding and to communicate deficiencies to appropriate personnel; to train workers in safe work practices and observe compliance in the use of machine guards; to provide care to workers injured by machines; and to reinforce safe work practices among machine operators.

Accidents, Occupational↗