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Biomedical subjects

A Curley

Publications and source records attributed to A Curley.

At least 19 recordsLinked to original sources
PubMed2005

A family with autosomal dominant hypocalcaemia with hypercalciuria (ADHH): mutational analysis, phenotypic variability and treatment challenges.

Autosomal dominant hypocalcaemia with hypercalciuria (ADHH) is an intriguing syndrome, in which activating mutations of the calcium sensing receptor (CaSR) have recently been recognised. We describe a kindred with seven affected individuals across three generations, including patients affected in the first decade of life. Age at diagnosis varied from birth to 50 years. Affected members had hypocalcaemia (1.53-1.85 mmol/l), hypercalciuria, low but detectable parathyroid hormone (PTH) and hypomagnesaemia. Four of seven affected individuals were symptomatic (seizures, abdominal pains and paraesthesias), unrelated to severity of hypocalcaemia. Additional complications include nephrocalcinosis (n = 3) and basal ganglia calcification, identified by CT scanning in all five individuals. Symptomatic individuals were treated with calcium and calcitriol to reduce the risk of hypocalcaemic seizures. DNA sequence analysis, identified a mutation in exon 3, codon 129 (TGC-->TAC) of the CaSR gene of seven affected family members, resulting in loss of a conserved cysteine residue, potentially disrupting CaSR receptor dimerisation. Thus, a novel mutation was identified in this family, who demonstrate variability of ADHH phenotype and also illustrate the complexities of clinical management. Optimal management of ADHH is difficult and we recommend judicious treatment to avoid an increased risk of nephrocalcinosis.

Adolescent↗
PubMed2003

Screening of lower back pain, low back pain clinic. The clinical experience.

Acute low back pain is a common complaint with high prevalence in society. Orthopaedic and specialist spinal services may be overwhelmed by large numbers of patients with low back pain who do not require investigation or surgical intervention. This phenomenon has led to the establishment of back pain screening clinics as a system of triage for those with acute low back pain. In March 2001, a back pain screening clinic was established in the Adelaide and Meath Hospitals incorporating the National Children's hospital. Six hundred and sixty-five patients were seen in the first year of this clinic. Of these, only ninety-six required referral to the orthopaedic spinal clinic. Just twenty-nine of these patients required surgical intervention. The introduction of this service resulted in a reduction in the waiting periods for the specialised spine clinic. We conclude that back pain screening clinics result in a clinical and economical improvement in the care of those suffering from acute low back pain. This is achieved by the systematic and efficient assessment, treatment and referral of patients afflicted with acute low back pain.

Adult↗
PubMed2001

Mutational analysis in X-linked spondyloepiphyseal dysplasia tarda.

Spondyloepiphyseal dysplasia tarda (SEDT) is an X-linked recessive disorder characterized by short stature due to defective growth of the vertebral bodies. In addition, deformities of the femoral heads result in early onset secondary osteoarthritis of the hips. The disorder affects males only with heterozygous female carriers showing no consistent abnormalities. The gene causing SEDT, which is located on Xp22.12-p22.31, consists of 6 exons of which only exons 3, 4, 5, and 6 are translated to yield an 140 amino acid protein, referred to as SEDLIN. SEDLIN mutations have been observed in SEDT patients, and we have undertaken studies to characterize such mutations in four unrelated SEDT kindreds by DNA sequence analysis. We identified two nonsense and two intragenic deletional frameshift mutations. The nonsense mutations occurred in exons 4 (TGG-->TGA, Trp70Stop) and 6 (CGA-->TGA, Arg122Stop). Both of the intragenic deletions, which were approximately 750 bp and 1300-1445 bp in size, involved intron 5 and part of exon 6 and resulted in frameshifts that lead to premature termination (Stop) signals. Thus, all four mutations are predicted to result in truncated proteins. The results of our study expand the spectrum of SEDLIN mutations associated with SEDT, and this will help to elucidate further the role of this novel protein in the etiology of this form of osteochondrodysplasia.

Codon, Nonsense↗
PubMed1994

How case management can improve the quality of patient care.

In January 1993, The New York Hospital Medical Center of Queens, a 487 bed acute care teaching hospital, created a Case Management Department to provide quality health care for patients that was cost efficient and at the same time reduce length of stay. Registered nurses with extensive medical and surgical expertise who were quality assurance/utilization coordinators and discharge planning nurses were cross-educated to become patient case managers. The case manager coordinates patients care services to improve the quality of the total patient experience. Reviews are conducted daily. The case managers indicate quality issues on their computer worksheets. Quality concerns are addressed and referrals made to the QA Department. Case Management Team rounds are conducted on the patient unit to discuss quality issues and barriers to discharge. Many delays were noted in patient care services i.e. Physical Therapy (P.T.) and Radiology. Readmissions within 48 hours of discharge were noted and reviewed as an indicator to monitor outcome and quality concerns. Continuous Quality Improvement (CQI) projects were initiated to reduce patient care delays. Multidisciplinary teams were formed to expedite solutions. The number of P.T. and Radiology delays were dramatically reduced through the CQI process. The case manager's role is vital to the delivery of quality patient care and containment of ever spiraling health care costs.

Hospital Bed Capacity, 300 to 499↗
PubMed1983

Six-month daily treatment of sheep with neurotoxic organophosphorus compounds.

The delayed neurotoxic effects of tri-o-cresyl-phosphate (TOCP), O-methyl-O-(4-bromo-2,5-dichlorophenyl) phenylphosphonothioate (leptophos), and O-ethyl O-(4-nitrophenyl) phenylphosphonothioate (EPN) at 5, 5, and 1 mg/kg/day, respectively, on male sheep were studied during 6 months of daily oral treatment under field conditions. A vehicle-control group of sheep given corn oil (0.1 ml/kg/day) only was used for comparison. All sheep were killed 24 h after the 180th daily treatment. Blood, brain, spinal cord, and sciatic nerve tissues were taken for histological and/or biochemical examinations. The results indicated that leptophos induced severe ataxia and paralysis in sheep following about 4 months of treatment. TOCP produced either mild ataxia or lameness in two of four sheep during the last week of experiment. On the other hand, none of the EPN-treated sheep showed clinical signs of neurotoxicity during the course of the experiment at the dosage tested. These clinical results were supported by histological findings and also by biochemical results with neurotoxic esterase (NTE) measurements. In the case of leptophos-treated sheep, numerous prominent degenerative lesions of axons were observed in spinal cords and brains. Similar but somewhat less numerous lesions were noted in sheep treated with TOCP. No histological changes were observed in similar tissues taken from EPN-treated sheep. The results also indicated that, for chronic exposure to these neurotoxic organophosphorus compounds in sheep, a threshold in excess of 60-70% prolonged inhibition of brain NTE, or 50-60% inhibition of spinal cord NTE must be exceeded to initiate clinical and/or histological neurotoxic effects.

Acetylcholinesterase↗
PubMed1982

Is delayed neurotoxicity a property of all organophosphorus compounds? A study with a model compound: parathion.

A recently reported hypothesis of other investigators that the induction of delayed neurotoxicity is a property of all organophosphorus compounds including parathion was evaluated in light of the inability of parathion to induce in our laboratory any clinical, histological, or biochemical signs of delayed neurotoxicity in hens following a very intensive dosing regimen. Parathion was administered orally or applied dermally as 1 mg/kg/day for 1 week and then the dose was increased by 1 mg/kg/day at weekly intervals up to 6 mg/kg/day which was given thereafter until a total of 90 doses. Results indicate that parathion either orally or dermally did not produce delayed neurotoxicity in hens comparable to that induced by tri-orthocresyl phosphate (TOCP) in this experiment. This finding is supported by clinical, histological, and biochemical evidences. No clinical signs or histopathological changes in spinal cords and sciatic nerves of the type associated with delayed neurotoxicity were observed in any of the surviving parathion-treated hens. Moreover, this extensive treatment with parathion resulted in no significant in vivo effect on neurotoxic esterase, an esterase believed to be the initial target in the genesis of delayed neurotoxicity. These results agree with the general hypothesis that delayed neurotoxicity is a special toxic effect of some but not all of the organophosphorus esters.

Acetylcholinesterase↗
PubMed1982

Species susceptibility to delayed toxic neuropathy in relation to in vivo inhibition of neurotoxic esterase by neurotoxic organophosphorus esters.

Tri-o-cresyl phosphate (TOCP) and O-ethyl O-(4-cyanophenyl) phenylphosphonothioate (cyanofenphos, Surecide) were found to be delayed neurotoxicants. They were administered to chickens by gavage at 100 and 30 mg/kg . d for 15 d, respectively. In CD-1 mice neither TOCP nor cyanophenphos induced any of the usually recognized clinical symptoms of neuropathy when administered daily by gavage at 262 or 31.25 mg/kg . d for 30 d, respectively. In the chickens, TOCP and cyanofenphos produced about 98 and 90% in vivo inhibition of brain neurotoxic esterase (NTE) activity. In the mice, 24 h after the last daily dose, TOCP and cyanofenphos produced only about 50 and 40% in vivo inhibition of the brain NTE activity. Parathion [O,O-diethyl O-(4-nitrophenyl) phosphorothioate], at 2 or 6.75 mg/kg . d for 15 or 30 d, did not induce neuropathy in either chicken or mice and produced no significant in vivo inhibition of brain NTE activity at the end of the dosing regimen. The specific activity of NTE in control chicken brain crude homogenate was much higher than that in mouse brain homogenate. These results suggest that the differences between chickens and mice in susceptibility to neurotoxic organophosphates may be attributed to (1) inhibitor specificity of NTE forms in the brain in these two different animal species and/or (2) inability of the active metabolites of these neurotoxic compounds to reach the site of action.

Animals↗
PubMed1981

A direct method to assay neurotoxic esterase activity.

A direct photometric method for assaying neurotoxic esterase (NTE) activity of chicken brain microsomal preparation has been developed using 4-nitrophenyl esters as substrates. Paired samples of the microsomal preparation were preincubated for 20 min with paraoxon plus either (a) buffer or (b) mipafox before addition of substrate. The initial rate of NTE activity was directly recorded at 410 nm by matching the content of tube (a) against tube (b) after addition of the substrate to both of them. The 4-nitrophenyl esters of propionic, butyric, valeric, lauric, capric and caproic acids were tested as substrates. Results indicated that 4-nitrophenyl valerate and caproate, respectively, are the most hydrolyzable substrates for NTE with this method; its also enables detailed kinetic studies of NTE to be made. The Michaelis constant (Km) for the hydrolysis of 4-nitrophenyl valerate by NTe was found to be 5.55 . 10(-5) M.

Animals↗
PubMed1981

Biochemical interaction of six OP delayed neurotoxicants with several neurotargets.

Five organophosphorous insecticides: Leptophos, EPN, Cyanofenphos, trichloronate and salithion proved to cause irreversible ataxia not only to chicken but also to mice and sheep. TOCP was included as a reference. Cyanofenphos blocked the catecholamine B-receptor binding activity with 3H-norepinephrine at a level similar to that of the specific inhibitor propranolol in the mouse heart preparation. In the lamb heart preparation, the B-receptor was more sensitive to Leptophos, salithion and TOCP than to propranolol. The six compounds and their oxons were screened for their in-vitro inhibition to monamine oxidase (MAO), acetyl cholinesterase (AChE) and neurotoxic esterase (NTE) in the brain of either mouse, lamb or chicken. It is believed that their AChE inhibition stands for their acute toxicity, while NTE inhibition is responsible for their paralytic ataxia.

Animals↗
PubMed1977

Hexachlorophene storage in a burn patient associated with encephalopathy.

Hexachlorophene (HCP), a chlorinated phenolic hydrocarbon with bacteriostatic properties against Staphylococcus, is used in a number of topical products. Absorption through normal and damaged human skin has been appreciated and neurologic changes have been described in experimental animals, but instances of human toxicity have been reported infrequently. A 10-year-old boy who sustained a 25% burn did well initially but died in the second week of convalescence with hyperthermia, lower-extremity weakness, and cerebral edema. His treatment had included frequent applications of HCP. Analysis of post-mortem tissue revealed the presence of toxic levels of HCP in the blood (2.2 mug/gm) and brain (2.2 mug/gm), with storage in skin (25 mug/gm), liver (4.4 mug/gm), and fat (6.0 mug/gm). This case suggests that topical applications of HCP in man may result in an extensive absorption with fat storage and may cause fatal encephalopathy.

Brain Diseases↗