Prediagnostic toenail cadmium and zinc and subsequent prostate cancer risk

BACKGROUND: Cadmium is a recognized human lung carcinogen that has also been positively associated with prostate cancer mainly in occupationally exposed men. The association between dietary and supplemental zinc intake and prostate cancer has not been consistent in epidemiologic studies. We evaluated the association between prediagnostic toenail cadmium and zinc concentrations and risk of prostate cancer in a cohort in which the primary route of exposure to cadmium and zinc is the diet. METHODS: Included in the analysis were 115 prostate cancer cases and 227 age-matched controls nested in the prospective CLUE II study located in Washington County, MD. Participants provided toenail samples at baseline in 1989. Furnace atomic absorption and flame atomic absorption were used to determine toenail cadmium and zinc concentrations, respectively. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from conditional logistic regression models. RESULTS: Median toenail cadmium and zinc concentrations did not statistically significantly differ between prostate cancer cases (cadmium, 45.9 ppb; zinc, 155.3 ppm) and controls (cadmium, 54.5 ppb; zinc, 164.0 ppm). Prostate cancer risk did not increase with increasing concentrations of cadmium (P trend = 0.9) and did not decrease with increasing concentrations of zinc (P trend = 0.2). For both metals, the ORs for the top four fifths were each below 1.0 when compared with the bottom fifth. CONCLUSION: Men who have high toenail cadmium concentrations in the range observed in this general population sample were not at an increased risk for prostate cancer. Although there was no evidence of a linear dose-response, these findings suggest that risk of prostate cancer may be slightly lower among men with moderate and higher zinc intake.     

A randomised,controlled trial of cemented versus cementless press-fit condylar total knee replacement. Ten-year survival analysis

We have carried out a long-term survival analysis of a prospective, randomised trial comparing cemented with cementless fixation of press-fit condylar primary total knee replacements. A consecutive series of 501 replacements received either cemented (219 patients, 277 implants) or cementless (177 patients, 224 implants) fixation. The patients were contacted at a mean follow-up of 7.4 years (2.7 to 13.0) to establish the rate of survival of the implant. The ten-year survival was compared using life-table and Cox's proportional hazard analysis. No patient was lost to follow-up. The survival at ten years was 95.3% (95% CI 90.3 to 97.8) and 95.6% (95% CI 89.5 to 98.2) in the cemented and cementless groups, respectively. The hazard ratio for failure in cemented compared with cementless prostheses was 0.97 (95% CI 0.36 to 2.6). A comparison of the clinical outcome at ten years in 80 knees showed no difference between the two groups. The survival of the press-fit condylar total knee replacement at ten years is good irrespective of the method of fixation and brings into question the use of more expensive cementless implants.     

Horner's syndrome and trigeminal nerve palsy after lumbar epidural analgesia for labor and delivery

This report highlights transient Horner's syndrome and trigeminal nerve palsy following labor epidural analgesia. A 29-year-old primigravida had a lumbar epidural catheter placed for analgesia in labor. The analgesia was maintained by infusion of a dilute local anesthetic/opioid mixture and turned off after achieving complete cervical dilation. Approximately 1 hour after delivery she complained of heaviness in her left eyelid, and was noted to have left-sided ptosis and paresthesia within the distribution of the ophthalmic and maxillary divisions of the trigeminal nerve, which resolved over the next 2 hours. There were no other neurologic changes. Horner's syndrome and cranial nerve palsies can occur as a consequence of epidural analgesia for labor.     

Counseling and rehabilitation

Counseling is an art learned over a lifetime, from other physicians during formal training and from one's personal counseling experiences. The effort to develop this art will be greatly appreciated and richly awarded with personal satisfaction. The importance of counseling and rehabilitation for the ocular trauma victim is in treating the whole patient, not only the injured eye. Every effort should be made to help a patient achieve a positive attitude about his or her capabilities to successfully use residual vision and live a full and enjoyable life as a visually impaired person.     

Induction of differential patterns of local cerebral glucose metabolism and immediate-early genes by acute clozapine and haloperidol

Atypical antipsychotic drugs, such as clozapine, show many differences in their actions as compared to typical antipsychotic drugs, such as haloperidol. In particular, the neuroanatomical substrates responsible for the superior therapeutic profile of clozapine are unknown. In order to identify regions of the CNS which are affected either differentially or in parallel by clozapine and haloperidol, we have used 2-deoxyglucose autoradiography to monitor local cerebral glucose utilisation (LCGU), in parallel with in situ hybridisation to monitor the expression of five immediate-early genes (c-fos, fos B, fra 1, fra 2 and zif 268). Clozapine (20 mg/kg i.p.) caused a reduction in LCGU in many areas of the psychosis-related corticolimbothalamic and Papez circuits, such as the anterior cingulate and retrosplenial cortices and the mammillary body. Haloperidol (1 mg/kg i.p.) showed less ability to modulate LCGU in these regions. Clozapine also increased immediate-early gene expression in these limbic circuits, although the pattern of induction was different for each gene, and also differed from the pattern of effects on LCGU. The only region which displayed similar effects with both antipsychotics was the anteroventral thalamus, with LCGU and c-fos mRNA expression being altered similarly by both drugs. This further supports the hypothesis of the thalamus being a common site of antipsychotic action. Since the Papez circuit has been implicated in emotive learning, and to be involved in mediating the negative symptoms associated with schizophrenia, the greater action of clozapine on regions within this circuit may also provide clues to the atypical antipsychotic's superior efficacy against negative symptoms.This is one of the first studies which provides a direct comparison of regional activity as assessed by LCGU and by a panel of IEGs. The results emphasise the necessity of monitoring a number of different parameters of regional activity in order to identity the neuroanatomical substrate for actions of a drug in the CNS.     

Relationship between exposure duration,tissue residues,growth, and mortality in rainbow trout (Oncorhynchus mykiss) juveniles sub-chronically exposed to copper

We conducted a 56-day sub-chronic test on the effects of Cu on rainbow trout (Oncorhynchus mykiss) fry at a nominal water hardness of 100 mg l(-1) (as CaCO(3)). Response measures were growth, whole body Cu concentrations, and mortality. Significant mortality was observed in fish exposed to 54.1 microg Cu l(-1) (47.8%) and 35.7 microg Cu l(-1) (11.7%). Growth was dose-dependent over the range of Cu treatments (0-54 microg Cu l(-1)), and was modeled as a function of Cu exposure concentration and exposure duration. Calculated inhibition concentrations (based on change in wet weight through a 56-day Cu exposure) were IC(50)=54.0 microg Cu l(-1), IC(20)=21.6 microg Cu l(-1), IC(10)=10.8 microg Cu l(-1), and IC(01)=1.1 microg Cu l(-1). Measured whole body Cu was also dose-dependent, and growth of trout fry was readily modeled as a function of tissue Cu and exposure duration. This model was virtually identical to a model previously developed for rainbow trout exposed to Cu at a hardness of 25 mg l(-1). Following the 56-day exposure period, we performed a 96-h acute challenge to Cu and Cd to evaluate the effects of Cu acclimation on acute Cu and Cd toxicity. Sensitivity to Cu was dependent on the 'acclimation dose'; trout previously held in control aquaria (i.e. not acclimated to Cu) suffered over 80% mortality, whereas trout previously exposed to 35.7 microg Cu l(-1) for 56 day suffered 20% mortality. These fish also showed somewhat reduced sensitivity to Cd, suggesting acclimation to Cu can enhance tolerance to other metals. Finally, the relationship between growth response and hardness (derived from several studies) appeared to have a different slope than the hardness relationship previously observed for lethality responses.     

Pharmacokinetic interaction between tacrolimus and diltiazem: dose-response relationship in kidney and liver transplant recipients

OBJECTIVE: To study the dose-response relationship of the pharmacokinetic interaction between diltiazem and tacrolimus in kidney and liver transplant recipients. DESIGN: Nonrandomised seven-period stepwise pharmacokinetic study. PATIENTS: Stable kidney (n = 2) and liver (n = 2) transplant recipients maintained on oral tacrolimus twice daily but not taking diltiazem. METHODS: Patients were treated with seven incremental dosages of diltiazem (0 to 180 mg/day) at > or = 2-weekly intervals. At the end of each interval, 13 blood samples were taken over a 24-hour period to allow determination of morning (AUC(12)), evening (AUC(12-24)) and 24-hour (AUC(24)) areas under the concentration-time curve for tacrolimus, as well as AUC(24) for diltiazem and three of its metabolites. RESULTS: There was considerable interpatient variability in tacrolimus-sparing effect. In the two kidney transplant recipients, an increase in tacrolimus AUC(24) occurred following the 20 mg/day dosage of diltiazem (26 and 67%). The maximum increase in tacrolimus AUC(24) occurred at the maximum diltiazem dosage used (180 mg/day), when the increase was 48 and 177%. In the two liver transplant recipients, an increase in tacrolimus AUC(24) did not occur until a higher diltiazem dosage (60 to 120 mg/day) was given. The increase at the maximum diltiazem dosages used (120 mg/day in one and 180 mg/day in the other) was also lower (18 and 22%) than that exhibited by the kidney transplant recipients. The increase in tacrolimus AUC(12) was similar to the increase in AUC(12-24) when diltiazem was given in the morning only (dosages < or = 60 mg/day). Hence, diltiazem affects blood tacrolimus concentrations for longer than would be predicted from the half-life of diltiazem in plasma. CONCLUSIONS: The mean tacrolimus-sparing effect of diltiazem was similar in magnitude to the cyclosporin-sparing effect previously reported. Whether the lesser tacrolimus-sparing effect with diltiazem seen in the liver transplant recipients was due to functional differences in the transplanted liver is not known, but it was not due to lower plasma diltiazem concentrations. Diltiazem makes a logical tacrolimus-sparing agent because of the potential financial savings and therapeutic benefits. Because of interpatient variability, the sparing effect should be demonstrated in each patient and not merely assumed.