Pyrophosphohydrolase activity and inorganic pyrophosphate content of cultured human skin fibroblasts. Elevated levels in some patients with calcium pyrophosphate dihydrate deposition disease.

In calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, metabolic abnormalities favoring extracellular inorganic pyrophosphate (PPi) accumulation have been suspected. Elevations of intracellular PPi in cultured skin fibroblasts from a single French kindred with familial CPPD deposition (19) and elevated nucleoside triphosphate pyrophosphohydrolase activity (NTPPPH), which generates PPi in extracts of CPPD crystal-containing cartilages (14) favor this suspicion. To determine whether NTPPPH activity or PPi content of cells might be a disease marker expressed in extraarticular cells, human skin-derived fibroblasts were obtained from control donors and patients affected with the sporadic and familial varieties of CPPD (CPPD-S and CPPD-F) deposition. Intracellular PPi was elevated in both CPPD-S (P less than 0.05) and CPPD-F (P less than 0.01) fibroblasts compared with control fibroblasts. Ecto-NTPPPH activity was elevated in CPPD-S (P less than 0.01) but not CPPD-F. Intracellular PPi correlated with ecto-NTPPPH (P less than 0.01). Elevated PPi levels in skin fibroblasts may serve as a biochemical marker for patients with familial or sporadic CPPD crystal deposition disease; ecto-NTPPPH activity further separates the sporadic and familial disease types. Expression of these biochemical abnormalities in nonarticular cells implies a generalized metabolic abnormality.

Twice-daily dosing of valproate with divalproex.

Equivalent doses of enteric-coated divalproex were substituted for valproic acid in 15 epileptic patients who were on a three- or four-times-a-day dosing schedule. After 2 wk the dosing regimen was changed to twice-daily divalproex dosing, and plasma levels were determined during the 12-hr period after the morning dose. Peak absorption was reached at 4 hr; extended plateaus were noted thereafter. The mean fluctuation between low and high plasma values for the group was 46%, with a decrease of less than 50% of peak levels in 9 of the 15 patients at a sampling time just before the second dose. Breakthrough seizures did not occur as a result of twice-daily dosing.

Gastrointestinal tolerance of divalproex sodium.

Divalproex sodium (DS), a new enteric-coated preparation of valproate, was administered to 27 patients who had not tolerated valproate because of gastrointestinal symptoms. Twenty-three (85%) tolerated DS and continued therapy. Of 34 patients previously naive to valproate, DS therapy was discontinued in only 4 patients (12%) because of gastrointestinal intolerance. Enteric-coated DS tablets had fewer gastrointestinal effects than VA capsules. Although the absorption of DS was delayed, the bioavailability of VA capsules and DS tablets was equivalent. After oral doses, peak plasma levels occurred within 1 hour with VA and at 3 hours with DS. Seven patients were maintained on a twice-daily schedule of DS.

Valproate tremors.

We made accelerometric recordings of the tremor induced by valproic acid. The tremor was similar to essential tremor and appeared within a month of starting therapy. It was present at rest and exacerbated by action or antigravity positioning. There was no close correlation of tremor severity and plasma valproate level, but the tremor usually appeared at dosages greater than 750 mg per day. This tremor has appeared in 20 of 25 patients recently studied. In some patients the tremor is markedly active; however, others note only minimal tremor activity.

Treatment of valproate tremors.

Chronic valproate therapy induces symptomatic tremor in about 10% of patients. We studied the effects of propranolol, amantadine, diphenhydramine, benztropine, and cyproheptadine on these tremors in 19 patients by using serial accelerometric recordings. Propranolol was clearly the most therapeutic. Amantadine was moderately effective, but cyproheptadine, diphenhydramine, and benztropine gave little or no relief.

Selenium, zinc, and copper changes with valproic acid: possible relation to drug side effects.

Side effects of treatment with the anticonvulsant valproic acid (VPA) suggested the possibility of alteration of trace metal status. Administration of VPA for 1 week produced significant depletion of zinc and selenium in plasma of rats and a one-third reduction of hepatic selenium. Patients who were treated chronically, with VPA as the sole anticonvulsant medication, had decreased plasma selenium levels. Most cases of VPA-associated hepatotoxicity occur in children. This could be due to decreased selenium concentrations when mechanisms for protection against peroxidative damage are not fully developed.

Comparison of valproic acid and phenytoin in newly diagnosed tonic-clonic seizures.

Sixty-one newly diagnosed epileptic patients with generalized tonic-clonic, clonic, or tonic seizures were randomly allocated to treatment with valproate (VPA) and phenytoin (PHT). After 6 months, both drugs had been effective in preventing recurrence of seizures. Seventy-three percent of patients receiving VPA and 47% of patients receiving PHT had no recurrences. Side effects of either drug were mild. Laboratory abnormalities were similar for both drugs. Except for one PHT patient with toxic hepatitis, therapy was not discontinued.

Effects of adenosine on wavelength of premature atrial complexes in patients without structural heart disease.

Intravenous adenosine produced slight decreases in conduction times for premature atrial complexes but proportionally greater shortening of the functional refractory period. Decreased wavelength may provide a basis for transient atrial fibrillation, which is sometimes observed after adenosine administration.

Preliminary observations on the use of midodrine hydrochloride in the treatment of refractory neurocardiogenic syncope.

Recurrent episodes of neurocardiogenic syncope that occur without warning are a common cause of recurrent syncope that can be identified during head upright tilt table testing. While the use of beta blockers, theophyllines, fludrocortisone, disopyramide, and serotonin reuptake inhibitors can be useful in the prevention of episodes, some patients are either unresponsive to or poorly tolerant of these agents. We investigated the use of the peripheral alpha stimulating agent midodrine in preventing both tilt-induced and spontaneous neurocardiogenic syncope. Twenty-five patients (16 women, 9 men, mean age 30 +/- 23 years) with severe recurrent syncope and a positive head upright tilt table study (refractory to or intolerant of standard therapies) were placed on midodrine 5-10 mg orally three times per day, (two patients required 15 mg/day). Of these, twelve became asymptomatic and five had a marked reduction in symptoms. We conclude that midodrine may be an effective therapy in patients with recurrent neurocardiogenic syncope refractory to other forms of therapy.

Ecto-nucleoside triphosphate pyrophosphohydrolase activity and calcium pyrophosphate dihydrate crystal deposition disease.

Articular cartilage contains any ectoenzyme activity, NTP-PPH, which is capable of generating PPi from NTP substrates. The PPi generated is from the cleavage of the alpha-beta pyrophosphate bond of NTP and does not result from the effects of NTP catabolites. NTP-PPH activity is expressed on human skin fibroblasts in culture and is significantly increased in subjects with CPPD deposition. In addition, cultured fibroblasts from subjects with CPPD disease have higher intracellular PPi concentrations compared to cells from normals and patients with OA. These results support the hypothesis that alterations in PPi metabolism provide the metabolic basis for CPPD deposition.

Heparinization of biological vascular graft reduces fibrin deposition.

An alternative graft is needed for coronary bypass operations in patients lacking suitable autologous vessels. We therefore studied Denaflex, a biologic graft, in a dog ex-vivo shunt model to determine whether heparin treatment makes this graft less thrombogenic. Comparison was also made to Bioflow, a nonheparinized biologic graft. Fibrinogen deposition during high flow (593 +/- 202 ml/min) decreased from 672 +/- 467 ng/mm2 in nonheparinized Denaflex grafts to 448 +/- 298 ng/mm2 (p < 0.05) in heparinized Denaflex grafts. At low flow (117 +/- 13 ml/min), heparinization of Denaflex grafts similarly decreased fibrinogen deposition from 1102 +/- 601 ng/mm2 to 703 +/- 405 ng/mm2 (p < 0.05). At both flow rates fibrinogen deposition in Bioflow grafts was less than in nonheparinized Denaflex, but was similar to heparinized Denaflex grafts. Platelet deposition was not influenced by heparinization of Denaflex grafts and was similar among Denaflex and Bioflow preparations. Whether Denaflex performs acceptably in vivo as a xenograft requires extensive study.

Reentrant tachycardias. A look at where treatment stands today.

Cardiac dysfunction is not limited to the elderly. In fact, the forms of tachycardia discussed in this article usually begin before age 40. The authors summarize the mechanisms involved and the findings on electrocardiography that help identify the type of dysrhythmia in patients presenting with palpitations and other signs of possible cardiac disease. In addition, they describe the procedure that has revolutionized treatment for reentrant tachycardia: closed-chest radiofrequency catheter ablation.

Peripherally-inserted central catheters: challenges for hospital management.

The peripherally-inserted central catheter (PICC) is an established technology in home intravenous (IV) therapy and its use is increasing in hospital and home-health settings. Institutions introducing PICCs as another form of IV therapy will realize cost savings. However, challenges may be encountered. Implementation and education programs for staff, patients, and home caregivers will maximize the benefits of PICC use.

Back injury prevention interventions in the workplace: an integrative review.

The purpose of this integrative review is to describe the state of knowledge about the effect of worksite back injury prevention programs on selected study outcomes. Fifteen experimental and quasi-experimental studies published between 1987 and 1994 were identified through a comprehensive literature search. The research studies were reviewed and analyzed using a data collection abstracting tool. Four types of back injury prevention intervention programs were identified: back belts, back schools, exercise/flexibility training, and educational classes. Positive program outcomes were reported for all four program types; however, the back school and the exercise/flexibility training programs were studied more frequently and demonstrated a greater proportion of positive results than the other two program types. Conclusions should be viewed cautiously due to the small number of studies reviewed and their methodological limitations. Implications for occupational health nursing practice and future research related to worksite back injury prevention are offered.

Malignant pulmonary edema in a pregnant woman caused by cor triatriatum.

BACKGROUND: Undiagnosed maternal congenital heart disease can result in significant risks to both mother and fetus. When maternal symptoms and signs are atypical of preeclampsia, broadening the differential diagnosis and multidisciplinary consultation can lead to improved outcomes. CASE: A 24-year-old primiparous woman with a pregnancy complicated by elevated blood pressure and proteinuria presented at term with symptoms of decreased fetal movement, increasing dyspnea, and cough. Her symptoms progressively worsened until she experienced cardiorespiratory arrest during attempted intubation. Emergency cesarean delivery was performed after 5 minutes of resuscitation efforts. Echocardiogram performed after delivery revealed cor triatriatum requiring surgical excision. CONCLUSION: A complete differential diagnosis for edema, hypertension, and dyspnea near term will allow for recognition of more rare conditions. Referral to cardiology in cases in which work-up is negative for preeclampsia may aid in earlier diagnosis and management. A team approach to management involving obstetrics and medicine will improve the rapidity with which rare conditions can be managed effectively.