Synthesis of CuO nanoparticles stabilized with gelatin for potential use in food packaging applications.

In the present study, a method for the synthesis of gelatin-stabilized copper oxide nanoparticles was developed. Synthesis was carried out by direct chemical precipitation. Copper sulfate, chloride, and acetate were used as precursors for the copper oxide synthesis. Gelatin was used as a stabilizer. It was found that the formation of monophase copper oxide II only occurred when copper acetate was used as a precursor. Our results showed that particles of the smallest diameter are formed in an aqueous medium (18 ± 6 nm), and those of th largest diameter-in an isobutanol medium (370 ± 131 nm). According to the photon correlation spectroscopy data, copper oxide nanoparticles synthesized in an aqueous medium were highly stable and had a monomodal size distribution with an average hydrodynamic radius of 61 nm. The study of the pH effect on the colloidal stability of copper oxide nanoparticles showed that the sample was stable in the pH range of 6.8 to 11.98. A possible mechanism for the pH influence on the stability of copper oxide nanoparticles is described. The effect of the ionic strength of the solution on the stability of the CuO nanoparticles sol was also studied, and the results showed that Ca2+ ions had the greatest effect on the sample stability. IR spectroscopy showed that the interaction of CuO nanoparticles with gelatin occurred through the hydroxyl group. It was found that CuO nanoparticles stabilized with gelatin have a fungicidal activity at concentration equivalent 2.5 · 10-3 mol/L and as a material for food nanopackaging can provide an increase in the shelf life of products on the example of strawberries and tomatoes. We investigated the possibility of using methylcellulose films modified with CuO nanoparticles for packaging and storage of hard cheese "Holland". The distribution of CuO nanoparticles in the methylcellulose film was uniform. We found that methylcellulose films modified with CuO nanoparticles inhibited the growth and development of QMAFAM, coliforms, yeast and mold in experimental cheese sa mples. Our research has shown that during the cheese storage in thermostat at 35 ± 1 °C for 7 days, CuO nanoparticles migrated to the product from the film. Nevertheless, it is worth noting that the maximum change in the concentration of copper in the experimental samples was only 0.12 µg/mg, which is not a toxic concentration. In general, the small value of migration of CuO nanoparticles confirms the high stability of the developed preparation. Our results indicated that the CuO nanoparticles stabilized with gelatin have a high potential for use in food packaging - both as an independent nanofilm and as part of other packaging materials.

Aortic stiffness in normal and hypertensive pregnancy.

The objective of this study was to examine whether aortic stiffness, as assessed by pulse wave analysis, could reliably discriminate between normal and hypertensive pregnancies. One hundred pregnant women were studied: five with severe pre-eclampsia, 27 with gestational hypertension, 14 with chronic hypertension and 54 with normal pregnancy. Central hemodynamic parameters were obtained by an applanation tonometry and included central aortic systolic blood pressure (CSBP), central aortic diastolic blood pressure (CDBP), augmentation pressure (AP), augmentation index (AIx), AIx corrected to a heart rate of 75 (AIx@75) and time to reflection (Tr). All measures of aortic stiffness, including AP, AIx and AIx@75 were significantly higher in women with gestational hypertension and pre-eclampsia compared with normal pregnancies and women with chronic hypertension (p < 0.05 for all comparisons). There were no significant differences between normal pregnancies and women with chronic hypertension (p > 0.05 for all comparisons). Tr was significantly shorter in women with pre-eclampsia and gestational hypertension compared with normal pregnancies (p < 0.05). Aortic stiffness, as assessed by pulse wave analysis, is significantly increased in women with pre-eclampsia and gestational hypertension but not in treated women with chronic hypertension. Pulse wave analysis has a potential as a screening tool in women at high risk for pre-eclampsia. The final role of this method should be determined in prospective studies.

[The risks of combining medicine and herbal remedies].

The risks of using herbal remedies, considered 'natural', should not be disregarded, as some have serious side effects and some interact with and influence conventional medical therapeutics. The effect may be pharmacokinetic by altering absorption or metabolism, and may be pharmacodynamic, by changing the final effect of the drug. St. John's wort, for example, an antidepressant herbal remedy, may pharmacodynamically interact with specific serotonin reuptake inhibitors (SSRI's), causing a serotonin syndrome. St. Johns wort also causes serious pharmacokinetic interactions by activating the cytochrome CYP3A4, dangerously decreasing blood levels of cyclosporin, warfarin, and theophylline, and reducing the efficacy of contraceptive pills and AIDS therapy. The article presents a review of a number of herbal remedies, commonly used in Israel, that have documented drug interactions, providing details of common indications, adverse reactions and drug interactions of each herbal remedy. Physicians should recognize the fact that patients use herbal remedies, purchased directly at pharmacies or health stores, and be aware of the potential interactions of these remedies with conventional drugs.

L-NMMA (a nitric oxide synthase inhibitor) is effective in the treatment of cardiogenic shock.

BACKGROUND: The objective was to assess the safety and efficacy of L-NMMA in the treatment of cardiogenic shock. METHODS: We enrolled 11 consecutive patients with cardiogenic shock that persisted after >24 hours from admission, despite coronary catheterization and primary percutaneous transluminal coronary revascularization, when feasible, and treatment with mechanical ventilation, intraaortic balloon pump (IABP), and high doses of catecholamines. L-NMMA was administered as an IV bolus of 1 mg/kg and continuous drip of 1 mg. kg(-1). h(-1) for 5 hours. Treatment with catecholamines, mechanical ventilation, and IABP was kept constant throughout the study. RESULTS: Within 10 minutes of L-NMMA administration, mean arterial blood pressure (MAP) increased from 76+/-9 to 109+/-22 mm Hg (+43%). Urine output increased within 5 hours from 63+/-25 to 156+/-63 cc/h (+148%). Cardiac index decreased during the steep increase in MAP from 2. 0+/-0.5 to 1.7+/-0.4 L/(min. m(2)) (-15%); however, it gradually increased to 1.85+/-0.4 L/(min. m(2)) after 5 hours. The heart rate and the wedge pressure remained stable. Twenty-four hours after L-NMMA discontinuation, MAP (+36%) and urine output (+189%) remained increased; however, cardiac index returned to pretreatment level. No adverse events were detected. Ten out of eleven patients could be weaned off mechanical ventilation and IABP. Eight patients were discharged from the coronary intensive care unit, and seven (64%) were alive at 1-month follow-up. CONCLUSIONS: L-NMMA administration in patients with cardiogenic shock is safe and has favorable clinical and hemodynamic effects.

High-dose intravenous isosorbide-dinitrate is safer and better than Bi-PAP ventilation combined with conventional treatment for severe pulmonary edema.

OBJECTIVE: To determine the feasibility, safety and efficacy of bilevel positive airway ventilation (BiPAP) in the treatment of severe pulmonary edema compared to high dose nitrate therapy. BACKGROUND: Although noninvasive ventilation is increasingly used in the treatment of pulmonary edema, its efficacy has not been compared prospectively with newer treatment modalities. METHODS: We enrolled 40 consecutive patients with severe pulmonary edema (oxygen saturation <90% on room air prior to treatment). All patients received oxygen at a rate of 10 liter/min, intravenous (IV) furosemide 80 mg and IV morphine 3 mg. Thereafter patients were randomly allocated to receive 1) repeated boluses of IV isosorbide-dinitrate (ISDN) 4 mg every 4 min (n = 20), and 2) BiPAP ventilation and standard dose nitrate therapy (n = 20). Treatment was administered until oxygen saturation increased above 96% or systolic blood pressure decreased to below 110 mm Hg or by more than 30%. Patients whose conditions deteriorated despite therapy were intubated and mechanically ventilated. All treatment was delivered by mobile intensive care units prior to hospital arrival. RESULTS: Patients treated by BiPAP had significantly more adverse events. Two BiPAP treated patients died versus zero in the high dose ISDN group. Sixteen BiPAP treated patients (80%) required intubation and mechanical ventilation compared to four (20%) in the high dose ISDN group (p = 0.0004). Myocardial infarction (MI) occurred in 11 (55%) and 2 (10%) patients, respectively (p = 0.006). The combined primary end point (death, mechanical ventilation or MI) was observed in 17 (85%) versus 5 (25%) patients, respectively (p = 0.0003). After 1 h of treatment, oxygen saturation increased to 96 +/- 4% in the high dose ISDN group as compared to 89 +/- 7% in the BiPAP group (p = 0.017). Due to the significant deterioration observed in patients enrolled in the BiPAP arm, the study was prematurely terminated by the safety committee. CONCLUSIONS: High dose ISDN is safer and better than BiPAP ventilation combined with conventional therapy in patients with severe pulmonary edema.

Coexistence of sporadic multiple endocrine neoplasia and scapular ectopic breast. Coincidence or biologically associated?

We describe a patient who presented with sporadic pheochromocytoma and parathyroid adenoma in the absence of medullary thyroid carcinoma, which coexisted with fully developed scapular ectopic breast tissue. If not coincidental, this association might support the concept that all components of multiple endocrine neoplasia type IIA originate from embryonic ectodermal tissue, and that sporadic multiple endocrine neoplasia type IIA, as well as ectopic breast tissue, may result from a noxious event at a critical embryonic stage.

Sibutramine in weight control: a dose-ranging, efficacy study.

We tested the safety and efficacy of sibutramine, 5 and 20 mg, and placebo on weight loss. Medication was added to caloric restriction, behavior modification, and exercise in a parallel-group, double-blind clinical trial. Participants were 130% to 180% of ideal body weight and in good health. The study lasted 12 weeks over Thanksgiving, Christmas, and New Year's Day. Weight loss during 8 weeks of study medication was: placebo, 1.4 +/- 2.1 kg (n = 19); 5 mg sibutramine, 2.9 +/- 2.3 kg (n = 18); and 20 mg sibutramine, 5.0 +/- 2.7 kg (n = 18) (p less than 0.05 sibutramine, 5 and 20 mg, versus placebo; p less than 0.05 sibutramine, 20 mg versus 5 mg). There is a significant dose-effect relationship. Five participants left the study before completion, all because of adverse events; placebo (one patient), 5 mg sibutramine (one patient), and 20 mg sibutramine (three patients). Sleep difficulties were noted by eight participants (20 mg sibutramine, seven patients; 5 mg, one patient; and placebo, no patients). Six of 21 participants receiving 20 mg complained of irritability, unusual impatience, or "excitation." Sibutramine, 5 and 20 mg, added to a multimodal program assisted participants in losing weight.

Hydrochlorothiazide-amiloride causes excessive urinary zinc excretion.

Serum zinc levels and urinary zinc excretion were compared in 15 patients with essential hypertension taking chronically a combination of hydrochlorothiazide and amiloride as monotherapy, eight patients maintained with hydrochlorothiazide alone, and eight control subjects. Serum zinc values were statistically comparable in all three groups. However, urinary zinc excretion was abnormally elevated in the two patient groups. In the dosage used, amiloride did not have a zinc-sparing effect.

The effect of sildenafil on gastric emptying in patients with end-stage renal failure and symptoms of gastroparesis.

BACKGROUND: Delayed gastric emptying is a common disorder among patients with end-stage renal failure (ESRF). Pyloric relaxation, a major determinant of gastric emptying, is a nitric oxide (NO)-mediated process. NO-induced smooth muscle relaxation is mediated through its second messenger cyclic guanosine monophosphate, which is broken by tissue phosphodiesterases (PDEs). Thus the inhibition of cyclic guanosine monophosphate breakdown by PDE inhibitors can potentiate NO-mediated responses and facilitate pyloric relaxation. In an animal model of diabetes mellitus, treatment with sildenafil (a PDE-5 inhibitor) restored NO-mediated pyloric relaxation and improved gastric emptying. The aim of our study was to examine the hypothesis that sildenafil may improve gastric emptying in patients with ESRF and symptoms of gastric paresis. METHODS: We studied 12 patients with ESRF (6 men; age range, 54-80 years; 5 with diabetic nephropathy; 4 +/- 1 years receiving long-term renal replacement therapy) after either placebo or a 25-mg tablet of sildenafil (Viagra; Pfizer Inc). Gastric emptying of a solid meal (one medium-sized fried egg mixed with 37 MBq [1 mCi] technetium Tc 99m phytate plus 1 slice of bread and 150 mL of water at the end of the meal) was assessed 1 hour after dosing by use of a single-headed camera. Images were acquired every 30 seconds for 90 minutes immediately after patients ate. RESULTS: The gastric emptying rate was decreased at baseline (after placebo), to 33% +/- 6% (normal, > or =50%). Treatment with sildenafil had no effect on gastric emptying rates after 90 minutes (from 33% +/- 6% after placebo to 30% +/- 6% after sildenafil, P =.9). CONCLUSIONS: Sildenafil did not improve gastric emptying in patients with ESRF and gastric paresis. Sildenafil may have opposing effects on gastric peristalsis (causing gastric relaxation) compared with its effects on pyloric relaxation. Studies combining sildenafil with prokinetic drugs are of interest.

Increased toxicity of high-dose furosemide versus low-dose dopamine in the treatment of refractory congestive heart failure.

OBJECTIVE: To evaluate the safety and efficacy of low-dose dopamine, high-dose furosemide, and their combination in the treatment of refractory congestive heart failure. METHODS: Twenty consecutive patients with refractory congestive heart failure were randomized to receive intravenous low-dose (4 micrograms/kg/min) dopamine combined with low-dose (80 mg/day) oral furosemide (group A; n = 7), intravenous low-dose dopamine with medium-dose furosemide (5 mg/kg/day through continuous intravenous administration; group B; n = 7), or high-dose furosemide (10 mg/kg/day through continuous intravenous administration; group C; n = 6). RESULTS: The three groups showed similar improvement in signs and symptoms of congestive heart failure, urinary output (2506 +/- 671 ml/24 hr, mean +/- SD) and weight loss (3.3 +/- 2.3 kg) after 72 hours of therapy. Mean arterial blood pressure (MAP) decreased by 14% +/- 8% and 15% +/- 6% in groups B and C, respectively, but increased by 4% +/- 15% in group A (p = 0.017). Renal function deteriorated significantly in groups B and C: creatinine clearance decreased by 41% +/- 23% and 42% +/- 23%, respectively, but increased by 14% +/- 35% in group A (p = 0.0074). MAP decrease was positively correlated with the decrease in creatinine clearance (r = 0.7; p = 0.0007). Patients in group B and C had more hypokalemia than group A. Two patients in group C sustained acute oliguric renal failure and one patient in group B died suddenly while sustaining severe hypokalemia. CONCLUSION: Combined low-dose intravenous dopamine and oral furosemide have similar efficacy but induce less renal impairment and hypokalemia than higher doses of intravenous furosemide taken either alone or with low-dose dopamine. The renal impairment induced by intravenous furosemide is probably related to its hypotensive effect in patients with refractory congestive heart failure.

Usefulness of losartan, captopril, and furosemide in preventing nitrate tolerance and improving control of unstable angina pectoris.

Sixty consecutive normotensive patients with unstable angina pectoris, who were on continuous intravenous isosorbide dinitrate (ISDN) treatment and had not previously received angiotensin II receptor antagonists, angiotensin-converting enzyme (ACE) inhibitors, or diuretics were randomly assigned to treatment groups receiving intravenous ISDN for 72 hours. No additional treatment was given to group A (n = 15). Captopril, in a test dose of 6.25 mg, and followed by 12.5 mg 3 times daily for 24 hours and 25 mg 3 times daily for the next 24 hours, was given to group B (n = 15). The same dose of captopril plus 40 mg of furosemide in the morning were given to group C (n = 15). Losartan, in a single dose of 25 mg/day and increased to 50 mg after 24 hours was given to group D (n = 15). Nitrate tolerance was evaluated at 24-hour intervals at trough levels of each of the drugs by administering intravenous ISDN (1 mg bolus dose every 4 minutes) and recording the total ISDN test dose required to decrease the mean arterial blood pressure by > or =10%. Treatment with continuous ISDN only (group A) induced nitrate tolerance. The ISDN (mean +/- SD) test dose was 3.5 +/- 1.8 mg at baseline, increasing to 4.9 +/- 2.4 mg at 24 hours, and 8.0 +/- 3.0 mg at 48 hours. The addition of increasing doses of captopril to the continuous ISDN treatment (group B) completely prevented nitrate tolerance. Losartan, however, did not attenuate nitrate tolerance at 24 hours and attenuated it only partially at 48 hours. The addition of furosemide to captopril had no further effect on nitrate tolerance. Of 15 patients in group A (ISDN only), 4 (27%) experienced recurrent ischemic events requiring urgent coronary catheterization. No such events were recorded in group B (captopril), but did occur in 1 patient in each of group C (captopril plus furosemide) and D (losartan) (p = 0.083). Thus, the addition of captopril to the ISDN treatment regimen prevented tolerance to nitrates and improved angina control with apparent safety. Losartan also decreased nitrate tolerance, although to a lesser extent, and also improved angina control. The addition of furosemide to captopril conferred no further benefit.

Zinc metabolism in patients treated with captopril versus enalapril.

Several zinc parameters were assessed in 13 patients with essential hypertension who were chronically taking only captopril (six subjects) or enalapril (seven subjects), as well as in six untreated hypertensives, and nine healthy controls. Serum zinc levels were comparable in all groups. Twenty-four-hour urinary zinc excretion was significantly increased in the captopril-treated patients compared with the other three groups. The zinc:creatinine ratio in 24-hour urine was significantly increased in both captopril and enalapril groups, but was significantly greater in the former. Although plasma zinc concentrations were comparable in all groups, red blood cell (RBC) zinc values were significantly decreased in the captopril group compared with the other three groups. We conclude that (1) although both captopril and enalapril produce renal zinc loss, this loss is far greater in patients receiving captopril; and (2) captopril administration over 3 months or more generates RBC zinc depletion.

Erythrocyte Na+, K+ and Ca2+, Mg(2+)-ATPase activities in hypertensives on angiotensin-converting enzyme inhibitors.

OBJECTIVE: To investigate erythrocyte membrane Na+, K(+)- and Ca2+, Mg(2+)-ATPase activities in newly diagnosed hypertensive patients before and after 2, 4, and 6 months of treatment with enalapril or captopril as monotherapy. METHODS AND RESULTS: Na+, K(+)-ATPase activity (nmol ATP hydrolysed/min per mg protein) rose by 6 months of treatment in both groups when values were compared in each treated group over time (4.5 +/- 0.8 to 9.9 +/- 1.2; 4.9 +/- 0.8 to 10.5 +/- 1.7, respectively, p < 0.001 for both). When the treated groups were compared with controls at each period of time, Na+, K(+)-ATPase activity was higher at months 4 and 6 (p < 0.001) for both groups, respectively). Ca2+, Mg(2+)-ATPase activity (nmol ATP hydrolyzed/min per milligram protein) in the absence and in the presence of calmodulin increased in the enalapril (6.4 +/- 0.7 to 8.9 +/- 0.95, p < 0.05; 13.4 +/- 1.2 to 17.2 +/- 1.2, p < 0.05, respectively) and captopril (7.0 +/- 0.6 to 8.5 +/- 0.7; 14.4 +/- 1.1 to 16.0 +/- 1.0, p < 0.05, respectively) groups after 6 months of treatment compared within each treated group over time. When patient groups were compared with controls at time 0, 2, 4, and 6 months, the pump activity was higher in the treated groups at 6 months. CONCLUSION: The long-term enhancement of cell membrane Na+, K(+)-and Ca2+, Mg(2+)-ATPase activity associated with enalapril and captopril therapy may represent a specific effect of these agents or alternatively, a nonspecific outcome of blood pressure reduction.

A prospective study of posttraumatic stress symptoms and nonadherence in survivors of a myocardial infarction (MI).

We examined a novel hypothesis that links symptoms of MI-related posttraumatic stress disorder (PTSD) to nonadherence. According to this hypothesis, patients who are traumatized by their medical illness do not take their medications as prescribed. As a part of the avoidance dimension of PTSD, patients who are traumatized may avoid being reminded of the MI by not taking the medication. MI survivors were prospectively followed for 6 months to 1 year. Adherence was assessed by pill count of Captopril. Demographic variables, medical risk factors, PTSD, and other psychiatric symptom dimensions were evaluated during follow-up. One hundred two of 140 recruited patients completed follow-up. Nonadherence to Captopril was associated with poor medical outcome (r=.93, P=.006). Above-Threshold PTSD symptoms were associated with nonadherence to medications (P=.05). No other psychiatric symptom dimensions were independently associated with nonadherence. Nonadherence to medications predicts adverse outcome during the first year after an acute MI. Nonadherence is associated with PTSD symptoms, which may either be a marker for or a cause of nonadherence. Treatment of PTSD may prove to be a useful approach for improving adherence.

Nephrectomy enhances interleukin 6 secretion by interleukin 1-stimulated mesangial cells in vitro.

BACKGROUND: Kidney mesangial cells are capable of producing and responding to interleukin 6 (IL-6) . In experimental glomerulonephritis mesangial cell proliferation correlates with increased IL-6 production. To investigate the involvement of IL-6 in post-nephrectomy compensatory hypertrophy, we studied the capacity of mesangial cells from single remaining kidneys to secrete IL-6 in culture. METHODS: Mesangial cells were obtained from uni-nephrectomized or sham-nephrectomized Charles River rats. Cell cultures were maintained for 8 days in DMEM/FI2HAM medium supplemented with IL-1 of interferon (IFN). IL6 production was measured using an IL-6-dependent B9 human hybridoma cell line. RESULTS: IL-6 production by mesangial cells from normal kidneys was significantly enhanced by IL-1, compared to unstimulated cells (p<0.01), and the increase was significantly greater in mesangial cells from a single remaining kidney (p<0.01). All cultures grown in control medium or with addition of IFN produced similar amounts of IL-6. CONCLUSION: Mesangial cells from single remaining kidneys in culture maintain an exaggerated capacity to produce IL-6 in response to IL-1. IL-6 was reported to enhance or inhibit mesangial cell proliferation in vitro. We suggest that the local over production of IL-6 by a single remaining kidney may play a role in regulating a sequence of physiological events in compensatory renal growth, initially stimulating mesangial cell proliferation and later blunting the process.

Conservative treatment for Brucella endocarditis.

Endocarditis is the most devastating complication of brucellosis. The accepted treatment for Brucella endocarditis (BE) is a combination of valve replacement and antibiotics. Conservative antibiotic treatment alone is not recommended by most authors, as it is considered ineffective, risking fatality. We describe a patient with BE, in whom antibiotic treatment alone resulted in complete recovery. On reviewing the literature, we found 12 additional such cases. We compared this group of 13 patients with data from 49 published cases treated with a combination of surgery and antibiotics, with a favorable outcome. Absence of congestive heart failure or a prosthetic valve, relatively mild extravalvular cardiac involvement, and a somewhat shorter disease history until initiation of treatment were characteristic of the group treated conservatively in comparison with patients who underwent surgery. In selected patients with BE, conservative antibiotic treatment may be a valid alternative to surgery.

Chylothorax following median sternotomy.

Reports of chylothorax (CT) following median sternotomy are rare, amounting so far to 16 cases in the English literature, of which 6 were cases of postcoronary artery bypass grafting (CABG). This report deals with an additional case of a 70-year-old woman who developed left pleural chylous effusion following CABG. It is suggested that the incidence of this type of pleural effusion is considerably greater than the few cases hitherto reported. Moreover, as CT may produce serious pulmonary and/or pleural functional impairment, it is proposed that a diagnostic tap be performed more often in cases of post CABG pleural effusion and that preventive drainage be instituted when CT is diagnosed.

Metabolic and clinical effects of oral magnesium supplementation in furosemide-treated patients with severe congestive heart failure.

BACKGROUND: Magnesium depletion and hypomagnesemia are common among furosemide-treated patients with chronic congestive heart failure. HYPOTHESIS: This investigation evaluated clinical and metabolic effects of oral magnesium supplementation. METHODS: Ten patients with severe congestive heart failure maintained on high dose furosemide (> or = 80 mg/day) received a supplement of oral magnesium citrate 300 mg/daily for 30 days. Clinical parameters were followed, and peripheral blood mononuclear cell magnesium and zinc content, serum and urine magnesium, potassium, zinc, calcium, phosphorus, and creatinine were assessed. RESULTS: Peripheral blood mononuclear cell magnesium content and serum potassium rose significantly at the end of the study (2.09 +/- 1.89 to 3.99 +/- 2.26 micrograms/mg cell protein, p < 0.05, and 4.17 +/- 0.38 to 4.39 +/- 0.27 mEq/l, p < 0.05, respectively), while the other parameters remained unchanged. CONCLUSION: In some of these patients, oral magnesium supplementation is effective in achieving substantial increments in intracellular magnesium and serum potassium which, in turn, may have cardioprotective effects.

Pharmacokinetics of intraperitoneal piperacillin/tazobactam in patients on peritoneal dialysis with and without pseudomonas peritonitis.

OBJECTIVE: The objective of this study was to assess the pharmacokinetics of intraperitoneal (IP) administration of the antibiotic combination piperacillin/tazobactam (PIP/TAZ) to patients on chronic ambulatory peritoneal dialysis (CAPD) with and without pseudomonas peritonitis. DESIGN: Open-labeled study. SETTING: The study was carried out in the CAPD unit of Assaf Harofeh Medical Center, Zerifin, Israel. PATIENTS AND METHODS: Six patients participated in the study, 4 had pseudomonas peritonitis, all were given an IP loading dose of 4 g/0.5 g PIP/TAZ. Twenty-four hours after the initial dose, a maintenance dose of 0.5 g/0.0625 g PIP/TAZ was administered with each dialysate exchange for a period of 1 week. The patients without peritonitis received only the loading dose. High performance liquid chromatography was used to determine the concentrations of PIPITAZ in plasma obtained at 0, 30, 60, 90, 120, 360, 480, 600, 720, and 1440 minutes after administration. Samples of the dialysate fluid for determination of PIP/TAZ concentration were collected at 6,10,14, 24, and 72, 120, and 168 hours. RESULTS: After the loading dose, the highest plasma PIP concentration (Cmax) was 51.6 t 21.25 Lig/mL and appeared at 1.5 = 0.45 hours (t,,a). During the maintenance period plasma PIP concentration was 5.2 t 4.75 Lg/mL. Tazobactam was detected in the plasma of 1 patient only. The concentration of TAZ in the dialysate fluid during the maintenance period was 2.3 t 0.5 ig/mL. CONCLUSIONS: Piperacillin administered IP at 4 g reached plasma concentrations comparable to intravenous administration and considered therapeutic (above the MIC90 for Pseudomonas aeruginosa) in CAPD patients with or without peritonitis. The maintenance dose, however, should be augmented. Tazobactam could not be detected in the plasma of most patients and the therapeutic implications of IP administration of TAZ cannot be directly correlated to intravenous administration.

Type II diabetes mellitus, congestive heart failure, and zinc metabolism.

Zinc status was assessed in patients with type II diabetes mellitus and congestive heart failure (CHF). Three groups of patients were enrolled into the study: Group 1: 15 patients with type II diabetes mellitus and CHF; Group 2: 20 patients with isolated type II diabetes mellitus; and Group 3: nine patients with isolated CHF. Twenty-four-hour urine was measured for creatinine, protein, and zinc, and blood was drawn for creatinine, proteins, liver enzymes, hemoglobin A1c, and zinc. Insulin treatment and hemoglobin A1c were comparable in the diabetic patients of groups 1 and 2, but group 1 was also treated with captopril and diuretics like the CHF patients of group 3. Plasma zinc levels were statistically similar in all three groups, but urinary zinc excretion (mumol/24 h) and urinary zinc: creatinine (mumol/mmol) ratio were significantly higher in the type II diabetics and CHF group (27.2 +/- 1.5; 1.69 +/- 0.6, respectively) compared to the diabetic patients alone (19.4 +/- 0.76; 0.97 +/- 0.3, respectively) and the CHF patients (9.7 +/- 0.3; 0.62 +/- 0.3, respectively). and the CHF patients (9.7 +/- 0.3; 0.62 +/- 0.3, respectively). Patients with type II diabetes mellitus and CHF were treated with higher doses of captopril than the CHF patients (56.25 +/- 24 mg vs 18.8 +/- 11 mg P < 0.05). Thus, patients with type II diabetes mellitus and CHF excrete larger amounts of zinc, which may eventually lead to zinc deficiency.