Autonomic cardiovascular control during a novel pharmacologic alternative to ganglionic blockade.

The purpose of this study was to compare ganglionic blockade with trimethaphan (TMP) and an alternative drug strategy using combined muscarinic antagonist (glycopyrrolate, GLY) and alpha-2 agonist (dexmedetomidine, DEX). Protocol 1: incremental phenylephrine was administered during control and combined GLY-DEX, or control and TMP on two control combined GLY and DEX or TMP infusion on two randomized days. Protocol 2: muscle sympathetic nerve activity (MSNA) and the baroreflex MSNA relationship was determined before and after GLY-DEX. Blood pressure was higher with GLY-DEX (99+/-3 mm Hg) and lower with TMP (78+/-3 mm Hg) relative to control (GLY-DEX: 90+/-2 mm Hg; TMP: 91+/-2 mm Hg; P<0.05). Incremental phenylephrine increased pressure during GLY-DEX (P<0.01 vs control) and TMP (P<0.01 vs control) to a similar degree. Both GLY-DEX and TMP infusion inhibited norepinephrine release (P<0.01 vs control). GLY-DEX inhibited baseline MSNA (P<0.05) and baroreflex changes in MSNA (P<0.01). We conclude that the GLY-DEX alternative drug strategy can be used as a reasonable alternative to pharmacologic ganglionic blockade to examine autonomic cardiovascular control.

Nicotine patch use in pregnant smokers: smoking abstinence and delivery outcomes.

OBJECTIVE: To describe smoking abstinence and fetal effects of pregnant smokers who received 8 weeks of nicotine patch therapy. METHODS: One-sample study of 21 pregnant women smoking > or = 15 cigarettes/day during their third trimester of pregnancy despite physician advice to stop. Nicotine patch therapy (22 mg/24 h) was initiated during the first day of a 4-day in-hospital study and continued for a total of 8 weeks. Subjects returned weekly until delivery, at 4 weeks after delivery, and at 6 and 12 months after patch therapy. Fetal growth and well-being were assessed using ultrasound examinations and non-stress tests. RESULTS: Eight of 21 subjects completed all 8 weeks of patch therapy according to the protocol. Five subjects (24%) discontinued using the nicotine patch, owing to adverse skin reactions. There were eight subjects (38%) who were biochemically confirmed abstinent from smoking at the time of delivery; of these, seven were continuously abstinent from the start of patch therapy. Centile weight for gestational age did not change significantly over time for 12 subjects with serial ultrasound measurements available at baseline, 4 weeks and 8 weeks following initiation of patch therapy. In all cases, non-stress tests remained reactive or became reassuring with observation. No significant preterm deliveries occurred (gestational ages of 36.3-41.1 weeks). Three infants suffered severe neonatal morbidity; however, these problems were unrelated to nicotine patch therapy. CONCLUSION: Nicotine patch therapy has potential benefit for pregnant smokers who continue to smoke despite physician advice to stop.

Performance characteristics of four free phenytoin immunoassays.

The measurement of the unbound or free phenytoin concentration is indicated in several situations, including uremia. In patients with uremia, metabolites of phenytoin and other substances accumulate and can displace phenytoin from its protein binding sites, with a consequent increase in the free fraction of drug. Some of the phenytoin metabolites that accumulate in uremia can cross-react with phenytoin immunoassays. In this study the authors evaluated four free phenytoin immunoassays compared with a high-performance liquid chromatography (HPLC) method: the Roche COBAS Integra, the Syva EMIT 2000, the Opus INNOFLUOR, and the Abbott TDx. All four methods demonstrated good precision, with interday coefficients of variation of < or = 5% and comparable recoveries using quality control material. Two of the methods, the EMIT 2000 and COBAS Integra, showed excellent agreement with the HPLC method using samples from patients both with normal renal function and with renal insufficiency. The other two methods, the INNOFLUOR and TDx, showed average positive biases for the therapeutic range of 3-7% and 21-22%, respectively, compared with the HPLC method for samples from patients with normal renal function, and average positive biases of 24-32% and 75-81%, respectively, with samples from patients with uremia.

Carbidopa/levodopa for smoking cessation: a pilot study with negative results.

The mesolimbic dopamine system is thought to be a critical substrate for drugs of addiction including nicotine. Since dopamine may play a critical role in mediating the reinforcing effects of nicotine, we hypothesized that administering levodopa in its therapeutic form (carbidopa/levodopa) might be effective for smoking cessation by replacing the effects of dopamine that smokers may seek during smoking. A pilot open-label study using carbidopa/levodopa for smokers wanting to stop smoking was carried out at the Mayo Clinic Nicotine Research Center, Rochester, MN. The dosing schedule was one tablet TID for 1 week, 1 1/2 tablets TID for 1 week, then two tablets TID for 6 weeks. Each tablet contained 25 mg of carbidopa and 100 mg of levodopa. The subjects were 40 adult smokers smoking > or = 20 cigarettes per day for 3 or more years. Self-reported abstinence from smoking was confirmed by expired air CO level of < or = 8 ppm. Nicotine withdrawal symptoms were assessed at baseline and daily during the medication phase. Smoking abstinence rates and withdrawal symptom relief were compared to the placebo (n = 153) arm of a previously reported bupropion smoking cessation trial. The biochemically confirmed, 7-day point-prevalence smoking abstinence rate at the end of carbidopa/levodopa treatment was 20.0% versus 19.0% for the placebo group (p > 0.10), and 12.5% of the carbidopa/levodopa group were abstinent versus 15.7% for the placebo group (p > 0.10) at 6 months. Subjects from both studies had significant increases in withdrawal scores from baseline, but there were no significant differences between the two groups at any time period. We found no differences in smoking abstinence rates or nicotine withdrawal symptom relief in smokers receiving carbidopa/levodopa compared to placebo. Despite the theoretical reasons why carbidopa/levodopa might be effective as a pharmacological adjunct in treating smokers, it was not observed in this group of smokers at this dose.

Effects of transdermal nicotine treatment on structure and function of coronary artery bypass grafts.

Smoking is a major risk factor for failure of coronary artery bypass grafts (CABG). Experiments were designed to determine effects of transdermal nicotine, independent of smoking, on structure and function of CABG. Saphenous veins were placed as CABG in untreated dogs (control) or in dogs treated with transdermal nicotine (one 11-mg or two 22-mg patches/day) for 5 wk. Serum nicotine and plasma nitric oxide were measured. Grafts were removed and prepared for organ chamber studies and histology. Serum nicotine averaged 12.1 and 118.7 ng/ml in the 11 mg/day and 44 mg/day groups, respectively. Plasma nitric oxide was higher in dogs treated with 11 mg/day doses compared with controls. In organ chamber studies, endothelium-dependent relaxations to thrombin and A-23187 and endothelium-independent relaxations to nitric oxide were greatest in grafts from dogs treated with 11 mg/day doses. Intimal thickness of the grafts were similar among groups. However, staining for bone sialoprotein was increased in the media of grafts from the 11 mg/day treatment group. These data suggest that transdermal nicotine in doses comparable and double to those used for conventional smoking cessation treatment in humans does not adversely affect early patency of canine CABG up to 4 wk postoperatively. Transdermal nicotine, however, may increase production of and response to nitric oxide in bypass grafts.

Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy.

Chronic transfusion therapy is being used more frequently to prevent and treat the complications of sickle cell disease. Previous studies have shown that the iron overload that results from such therapy in other patient populations is associated with significant morbidity and mortality. In this study we examined the extent of iron overload as well as the presence of liver injury and the predictive value of ferritin in estimating iron overload in children with sickle cell disease who receive chronic red blood cell transfusions. A poor correlation was observed between serum ferritin and the quantitative iron on liver biopsy (mean 13.68 +/- 6.64 mg/g dry weight; R = 0.350, P =.142). Quantitative iron was highly correlated with the months of transfusion (R = 0.795, P <.001), but serum ferritin at biopsy did not correlate with months of transfusion (R = 0.308, P =.200). Sixteen patients had abnormal biopsies showing mild to moderate changes on evaluation of inflammation or fibrosis. Liver iron was correlated with fibrosis score (R = 0.50, P =.042). No complications were associated with the liver biopsy. Our data suggest that, in patients with sickle cell disease, ferritin is a poor marker for accurately assessing iron overload and should not be used to direct long-term chelation therapy. Despite high levels of liver iron, the associated liver injury was not severe.

Nicotine patch use in pregnant smokers: nicotine and cotinine levels and fetal effects.

OBJECTIVE: The aims of this study were (1) to determine whether nicotine patch therapy for pregnant women smokers acutely compromises fetal well-being and (2) to determine the serum and urine nicotine and cotinine levels in pregnant women while smoking, while abstinent from smoking, and while receiving nicotine patch therapy compared with levels in a historical control group of nonpregnant women smokers who abstained from smoking while receiving comparable doses of nicotine patch therapy. STUDY DESIGN: Pregnant cigarette smokers (n = 21) aged >/=18 years whose fetuses were beyond 24 weeks' gestational age were recruited for this 1-sample, repeated-measures study. Serial measurements of the mother and fetus were made at baseline while the mother was smoking, while abstaining from smoking, and while using nicotine patch therapy for 4 days in a special care hospital unit. Nonpregnant women smokers of similar age were used for comparison. Morning and afternoon serum and 24-hour urine levels of nicotine and cotinine were obtained during hospitalization. Indicators of fetal well-being assessed were fetal heart rate and reactivity, systolic/diastolic ratio of blood flow in the umbilical artery, and fetal activity seen on ultrasonography and quantitated as biophysical profiles. RESULTS: No evidence of fetal compromise was seen during the inpatient phase while nicotine patch therapy was administered. Steady state (inpatient day 4) serum levels of nicotine were similar to smoking levels and to those seen in historical control subjects (ie, nonpregnant women of child-bearing age who were abstinent from smoking and who used the same nicotine patch). Morning serum cotinine levels were significantly higher (P =.038) in the nonpregnant subjects than in the pregnant subjects, whereas afternoon levels were not significantly different. Steady state urinary levels of nicotine and cotinine were also not significantly different in pregnant versus nonpregnant patients. On inpatient days 2, 3, and 4, when the women were not smoking and were wearing the nicotine patch, the morning fetal heart rates were significantly reduced relative to baseline when the subjects were smoking. CONCLUSIONS: Nicotine patch therapy was not found to be associated with indications of fetal compromise during the in-hospital phase of nicotine patch therapy in pregnant smokers who were abstaining. Although not conclusive because of the small sample sizes, serum nicotine levels (morning and afternoon) appear similar in pregnant and nonpregnant subjects and similar for both groups when smoking (baseline) as compared to the steady state of nicotine patch use.

Drug monitoring of antiretroviral therapy for HIV-1 infection: method validation and results of a pilot study.

BACKGROUND: Antiretroviral therapy for HIV-1 infection has become increasingly complex. The availability of new and potent drugs and progress in understanding the pathogenesis of HIV-1 infection have led to the establishment of new treatment paradigms. The varying dosing regimens, associated toxicities, and the potential for drug-drug and food-drug interactions further complicate treatment. This complexity contributes to patient nonadherence. Because clinicians have no tools to monitor adherence or drug-drug interactions and because response requires that therapy exceed the known inhibiting concentration, serum monitoring of antiretroviral therapy may play a role in improving treatment of HIV-1 infection. We report methods to quantify serum concentrations of antiretroviral drugs used to treat HIV-1 infection, precision and interference studies of these methods, and results observed in a pilot evaluation of blood serum concentrations from 12 human subjects. METHODS: HPLC offers adequate sensitivity to measure peak or trough serum concentrations of delavirdine, lamivudine, nevirapine, indinavir, nelfinavir, ritonavir, and saquinavir and peak serum concentrations of stavudine, zidovudine, and didanosine with reasonable precision. RESULTS: Peak indinavir serum concentrations in most patients were in the range of 1-10 mg/L, and trough concentrations were in the range of 0.1-0.5 mg/L. Peak stavudine concentrations were in the range of 0.3-1.3 mg/L, and trough concentrations were in the range of 0.1-0.5 mg/L. Peak zidovudine concentrations were in the range of 0.1-1.1 mg/L. CONCLUSIONS: Because this was a blood serum concentration-seeking pilot study to evaluate analytic performance, we do not report on the correlation of drug response to blood concentration. However, the concentrations observed in patients are generally consistent with blood concentrations reported from studies of monotherapy.

Measurement of blood serum cyclosporine levels using capillary "fingerstick" sampling: a validation study.

Capillary blood sampling as a means of monitoring blood cyclosporine levels has replaced venipuncture in some medical centers. As the validity of capillary venipuncture for analysis of cyclosporine has not been documented, we sought to validate the capillary blood collection technique by comparing it with serum samples collected simultaneously by venous phlebotomy. Forty paired capillary- and venous samples were collected from 36 cardiac transplantation patients and analyzed, using a polyclonal immunoassay. The values obtained were compared using regression correlation. The correlation coefficient for all 40 samples was 0.859. However, we discovered that the first 7 capillary specimens were processed incorrectly. The correlation coefficient for the other 33 samples was 0.995 (99% confidence interval 0.987-0.998). The excellent correlation between serum samples obtained from capillary sampling and from venous sampling, together with the ease of obtaining capillary blood specimens, make "fingerstick" sampling the method of choice for monitoring cyclosporine levels in infants and children.

Temporal effects of nicotine nasal spray and gum on nicotine withdrawal symptoms.

Nicotine nasal spray and nicotine gum have been found to be effective in relieving nicotine withdrawal symptoms. In this randomized single-blind study, 91 cigarette smokers were randomly assigned to a single 1 mg dose of active nicotine nasal spray (n=29), active 4 mg nicotine gum (n=31), saline placebo nasal spray (n=16) or placebo gum (n=15). Following overnight abstinence, subjects repeatedly completed visual analog scales for assessing nicotine withdrawal symptoms over 30 min preceding (time -30 min to time 0) and 120 min following a single dose of study medication. This sequence was performed 3 times during the day. Nicotine withdrawal symptoms were assessed on a 41-point visual analog scale (1=no withdrawal, 41=extreme withdrawal). At the initial session only, blood samples for serum nicotine levels were taken at baseline, then at 5, 10, 30 and 120 min following study drug administration. The mean (+/-SD) age of the subjects was 38.6 (+/-10.1) years, 48% were females, smoking rate was 24.5 (+/-7.8) cigarettes per day, and years of smoking was 19.9 (+/-10.0). A single 1 mg dose of nicotine nasal spray provided more immediate relief for craving for a cigarette compared to a single 4 mg dose of nicotine gum. Serum venous nicotine levels for the active nicotine nasal spray and nicotine gum were comparable at 5 and 10 min while the levels were higher for nicotine gum at 30 and 120 min. Changes in withdrawal symptoms were not found to be related to serum venous nicotine levels. Our findings provide a rationale for the as needed use of nicotine nasal spray to control withdrawal symptoms, possibly in combination with other medications with longer acting effects.

Clinical features and psychiatric comorbidity of subjects with pathological gambling behavior.

OBJECTIVE: Sociodemographic features, phenomenology, and psychiatric comorbidity of 30 subjects reporting pathological gambling behavior were examined. METHODS: Twenty-three men and seven women were recruited by advertisement and word-of-mouth. They all scored higher than 5 points on the South Oaks Gambling Screen, indicating problematic gambling behaviors. They completed structured and semistructured assessments, including the Diagnostic Interview Schedule for DSM-III-R disorders (DIS), the Personality Diagnostic Questionnaire, Fourth Revision (PDQ-IV), and the Minnesota Impulsive Disorders Interview. RESULTS: The typical subject was a 44-year-old white married man with a mean income of $34,250 who visited a casino once or more weekly. All 30 subjects reported gambling more money than they intended to. Twenty subjects (67 percent) reported gambling as a current problem, and nine (30 percent) reported it as a past problem. Twenty-one subjects (70 percent) wanted to stop gambling but did not feel they could. According to DIS results, 18 subjects (60 percent) had a lifetime mood disorder, 19 (64 percent) a lifetime substance use disorder, and 12 (40 percent) a lifetime anxiety disorder. Based on the PDQ-IV, 26 subjects (87 percent) had a personality disorder, the most common being obsessive-compulsive, avoidant, schizotypal, and paranoid personality disorders. The sample also had a relatively high rate of antisocial personality disorder. Impulse control disorders were common, especially compulsive buying and compulsive sexual behavior. CONCLUSIONS: The results confirm that individuals with pathological gambling suffer substantial psychiatric comorbidity. They support continued inclusion of pathological gambling in the diagnostic category of impulse control disorders.

Silicon analysis of breast and capsular tissue from patients with saline or silicone gel breast implants: II. Correlation with connective-tissue disease.

The silicone breast implant controversy rages on. Recent work has demonstrated that normal or baseline breast tissue silicon levels in women who had had no prior exposure to any type of breast implant may be as high as 446 microg/gm of tissue. These data ranged from 4 to 446 microg/gm of tissue, with a median of 27.0 microg/gm of tissue. In addition, numerous other epidemiologic and rheumatologic studies have demonstrated no association between silicone breast implants and any connective-tissue diseases. Despite these reports, the use of silicone implants remains restricted. The present study measured breast and capsular tissue silicon levels from 23 breasts in 14 patients with saline implants, and from 42 breasts in 29 patients with silicone implants. No patient in the saline implant group presented with signs or symptoms of connective-tissue disease. Patients with silicone implants, however, were divided into three groups based on the presence or absence of signs or symptoms of connective-tissue disease: group I, no symptoms or signs; group II, + symptoms, no signs; and group III, + symptoms, + signs. Six patients in group III were diagnosed with a specific connective-tissue disease, including systemic lupus erythematosus, rheumatoid arthritis, or scleroderma. The most common indications for implant removal or exchange were capsular contracture and implant rupture, although 41 percent of patients with silicone implants expressed media-related concern over the implant issue. The most common symptoms described by patients in groups II and III were joint pain and stiffness, arm pain and numbness, and fatigue. In all groups, capsular tissue silicon levels were significantly greater than breast tissue levels. This finding may indicate that the capsule serves as a barrier to the distribution of silicone from the implant into adjacent breast tissue. Although breast tissue silicon levels in patients with silicone implants were not significantly greater than those in patients with saline implants (p = 0.48), capsular tissue levels in patients with silicone implants were, indeed, significantly greater than those in patients with saline implants (p < 0.001). However, no statistically significant differences in tissue silicon levels were observed with relation to the presence or absence of connective-tissue disease signs or symptoms in patients with silicone implants (groups I to III). Therefore, these data strengthen the conclusion that there is no association between tissue silicon levels and connective-tissue disease.

Supporting pharmaceutical studies for FDA submissions: diversifying the drug monitoring laboratory.

Well-founded pharmacokinetic information is one of the cornerstones of a New Drug Application (NDA) to the Food and Drug Administration (FDA) required to introduce a new drug or a generic equivalent (ANDA) to the marketplace. The service that laboratories engaged in therapeutic drug monitoring provide to support clinical activities is also needed by the pharmaceutical industry during the evaluation and introduction of drugs to the marketplace. In considering this alternative service activity, one must be aware of and compliant with rules established by the FDA for performance of such studies. As specified in CFR 21, Parts 58, 211, and 320, good clinical and laboratory practice indicates that the laboratory should employ a Lab Study Director, who is responsible for the validation of all procedures implemented to support a study protocol, ensures that the laboratory carries out the study following these defined procedures, and personally reviews the results of all testing. The laboratory must validate each procedure by demonstrating and documenting that the procedure does what it is designed to do while meeting the analytical performance specifications required by the study. Laboratory records of all activities must be maintained and available for inspection by the FDA on request. The FDA has authority over all activities related to NDA and ANDA submissions and can bring criminal charges if results of a study are changed because a laboratory deviates from standard procedure. Competent drug monitoring laboratories are fully capable of participating in clinical trials testing activities. Laboratory staff should be fully versed in the FDA rules governing these activities, validate all procedures, and establish systems to verify the procedures are carried out as specified.

Hemosiderosis in cirrhosis: a study of 447 native livers.

BACKGROUND & AIMS: Hemosiderosis may have a detrimental effect on some chronic liver diseases. The aim of this study was to determine the prevalence and diagnostic implications of hemosiderosis in cirrhosis. METHODS: Tissue iron in 447 cirrhotic livers was studied histologically and chemically. RESULTS: Positive iron staining was found in 145 cases (32.4%), and increased chemical hepatic iron concentration was found in 91 cases (20.3%), including 38 cases (8.5%) with hepatic iron overload in the hemochromatosis range, defined by an iron index of > or = 1.9 (iron index equals hepatic iron concentration in micromoles per gram divided by age). However, homozygous hemochromatosis seemed to have caused the cirrhosis in only 5 instances. Stainable iron was found in 22%-67% of the cases with nonbiliary cirrhosis but in only 7%-20% of cases with biliary cirrhosis. Most available pretransplant biopsy specimens failed to show evidence of homozygous hemochromatosis. CONCLUSIONS: Iron overload is very common in many types of nonbiliary cirrhosis but rare in biliary cirrhosis. The hemosiderosis of affected livers seems to be acquired and to occur rapidly once cirrhosis has developed; cirrhosis alone may cause iron accumulation. In the presence of cirrhosis, hepatic iron indices of >1.9 should not be interpreted as proof of homozygous hemochromatosis.

Determination of silicon in breast and capsular tissue from patients with breast implants performed by inductively coupled plasma emission spectroscopy. Comparison with tissue histology.

A method for analysis of silicon in tissue was developed to determine silicon content in breast parenchymal and periprosthetic capsular tissues of patients with silicone or saline implants and to compare levels in tissues from normal (nonaugmented) breasts. It is of interest to determine whether increased silicon content in tissues can be associated with morbidity in patients who have received silicone implants. This manuscript addresses the issues involved in analysis of breast tissue samples for silicon and compares silicon levels with tissue histologic findings and patient morbidity. One hundred sixty tissue samples were obtained for silicon analysis from 72 patients during augmentation, capsulectomy with or without replacement mammoplasty, mastectomy, or biopsy procedures and were frozen in acid-washed polystyrene tubes at 220 degrees C until analysis. Samples were thawed, sectioned to approximately 0.1 g (dry weight), and digested in nitric acid before analysis by inductively coupled plasma emission spectroscopy, monitoring emission intensity at 251.6 nm. Tissue silicon levels (breast parenchymal and periprosthetic capsular tissue) in patients with silicone gel implants were much higher (mean, 9,287 micrograms/g, n = 106) than in patients with saline implants (mean, 196 micrograms/g, n = 37) or nonaugmented breasts (mean, 64 micrograms/g, n = 17). Histologic examination was performed on 54 tissue samples stained with hematoxylin-eosin. Tissue samples were rated as to degree of inflammation and calcification, and amount of giant cells, foamy histiocytes, and vacuoles containing a colorless refractory material. Vacuolization and foamy histiocyte ratings correlated significantly with tissue silicon concentration. No correlations were found between tissue silicon concentration and inflammation, calcification, or giant cell rating. Implant age (number of years an implant was in place before sampling) correlated with capsular tissue silicon concentration in patients with intact implants but not in those with ruptured implants. No difference in tissue silicon concentration was found between patients with or without signs or symptoms of morbidity. Using 0.1 g of tissue, the method was linear to 1,000 micrograms/g, and sensitivity was 3.7 micrograms/g. Precision between runs (mean, 5.1 micrograms/g; coefficient of variance, 13.7%; n = 13) was calculated from multiple analyses of a bovine liver standard (National Bureau of Standards, reference material 1577a). Significant biologic variability (21.4% to 52.5%) was seen in tissues with high silicon levels. Paraffin-embedded, formalin-fixed tissues are not amenable to silicon analysis by this method, because of leaching of silicone from the tissues during preparation. Thus only fresh frozen tissue samples were used.

Silicon analysis of breast and periprosthetic capsular tissue from patients with saline or silicone gel breast implants.

The ubiquitousness of silicon is well known. Recent work has demonstrated measurable baseline levels of silicon in nonaugmented cadavers, subsequent to numerous reports of significant elevations of such levels within patients with silicone breast implants and even more reports alleging a causal relation between silicone gel prostheses and connective-tissue diseases. Despite the lack of scientifically substantiated data that such a relation exists, the calamitous silicone breast implant controversy has ensued. Saline-filled breast implants are constructed with a silicone elastomer envelope that remains in direct contact with periprosthetic capsular tissue following implantation. Although there is no evidence to link saline implants with any disorders, it is important to know if saline breast implants contribute any silicon to human body baseline silicon levels. The present study measured tissue silicon levels in 28 breasts of 16 patients with saline-filled implants to determine if the silicone envelope of these prostheses can contribute to the elevation of such levels. These data were compared with data from 116 breasts of 65 patients with silicone gel-filled prostheses as well as breast tissue from 17 patients (controls) who had never been exposed to either type of implant. Samples of breast tissue and periprosthetic capsular tissue were obtained from patients with both intact and ruptured implants. Silicon levels of breast tissue specimens from patients with saline-filled implants were within the range of the controls if the implants were intact. Silicon levels in periprosthetic capsular tissue from patients with intact saline-filled implants were significantly higher than controls (p < 0.02); however, they were still 100-fold less than capsular tissue levels from patients with intact gel-filled implants. Silicon levels measured in both types of tissue were significantly elevated in patients with silicone gel-filled implants compared with controls (p < 0.01). In the case of ruptured gel implants, breast tissue demonstrated higher silicon levels than did similar specimens from patients with intact implants (p < 0.054); periprosthetic capsular tissue levels also were elevated, although the differences were not statistically significant (p = 0.54). These findings are independent of the implant brand or length of exposure to the particular prosthesis. The finding of elevated levels of silicon in both breast and periprosthetic capsular tissue in patients with silicone gel-filled implants in no way implies or substantiates any claim of a causal relationship between silicone and any reported illnesses.

The importance of urinary magnesium values in patients with gut failure.

OBJECTIVE: To determine whether urinary magnesium (Mg) values in patients with gut failure would be more helpful than serum Mg measurements in assessment of Mg deficiency. DESIGN: We compared serum and urinary Mg values in 16 patients with gut failure and 16 age- and sex-matched control subjects. MATERIAL AND METHODS: Sixteen patients with gut failure (nine women and seven men; mean age, 59 years) had serum and 24-hour urinary mg measured before Mg replacement therapy. Short bowel syndrome was present in 75%, and diffuse small bowel disease was present in 25%. RESULTS: The median value for serum Mg was 1.7 mg/dL for patients and 2.0 mg/dL for healthy control subjects (P < 0.001). The median values for urinary Mg were 19 mg and 127 mg per 24-hour specimen in patient and control groups, respectively (P < 0.001). A strong correlation was noted between serum Mg and urinary Mg levels. All patients had low urinary Mg values even though 9 of 16 (56%) had normal serum Mg values. Two patients with normal serum Mg concentrations had urinary Mg values of 20 mg/24 h (25% of normal). Serum, but not urinary, Mg correlated significantly with the length of remaining small bowel (P = 0.03). CONCLUSIONS: Urinary Mg declines before serum Mg and is an earlier and more reliable indicator of evolving Mg deficiency. On the basis of these observations and those showing beneficial effects of parenterally administered Mg supplements on urinary citrate excretion (and, presumably, formation of calcium oxalate stones), replacement of Mg in patients with gut failure should be targeted at normalizing urinary Mg.