Recent Publications by CFE Educators

Recent studies suggest that increased T-cell and autoantibody reactivity to lipids may be present in the autoimmune demyelinating disease multiple sclerosis. To perform large-scale multiplex analysis of antibody responses to lipids in multiple sclerosis, we developed microarrays composed of lipids present in the myelin sheath, including ganglioside, sulfatide, cerebroside, sphingomyelin and total brain lipid fractions. Lipid-array analysis showed lipid-specific antibodies against sulfatide, sphingomyelin and oxidized lipids in cerebrospinal fluid (CSF) derived from individuals with multiple sclerosis. Sulfatide-specific antibodies were also detected in SJL/J mice with acute experimental autoimmune encephalomyelitis (EAE). Immunization of mice with sulfatide plus myelin peptide resulted in a more severe disease course of EAE, and administration of sulfatide-specific antibody exacerbated EAE. Thus, autoimmune responses to sulfatide and other lipids are present in individuals with multiple sclerosis and in EAE, and may contribute to the pathogenesis of autoimmune demyelination.

BACKGROUND

Clinical guidelines for the treatment of primary hyperparathyroidism (pHPT) often suggest parathyroidectomy, but generally fail to consider neurocognitive and psychiatric symptoms because of the relative paucity of evidence.

METHODS

In this prospective study, patients with pHPT (PTX) and benign euthyroid thyroid disease (THY) referred for operation were evaluated pre- and postoperatively with validated psychometric and neurocognitive instruments to determine whether learning, memory, or concentration improved with after parathyroidectomy. Statistical comparisons between groups were performed with univariate analysis and repeated measures of analysis of variance.

RESULTS

Fifty-five subjects, mean age of 54 years, were evaluated preoperatively; 41 returned postoperatively. There were no significant differences between groups by age and gender. PTXs reported more depression symptoms preoperatively (P = .04) that improved postoperatively. There were no differences between the 2 groups on verbal memory and trait anxiety. For PTXs, average preoperative serum calcium concentration (11.3 mg/dL) and serum PTH level (100 pg/mL) normalized postoperatively. Preoperatively PTXs showed greater delays in their spatial learning (P = .03). All subjects learned across the 5 trials, but PTXs were more delayed (P = .03). After operation, PTXs improved and functioned at a level equivalent to the THYs. There was an interaction between trial (neurocognitive testing), visit (pre- vs postoperative), status (PTX vs THY), and change in PTH level (P = .06), suggesting that individuals with greater change in PTH were more likely to improve in their learning efficiency postparathyroidectomy.

CONCLUSIONS

PHPT may be associated with a spatial learning deficit and processing that improves after parathyroidectomy. While longer-term follow-up is necessary, neurocognitive symptoms perhaps should be considered as criteria for parathyroidectomy.

OBJECTIVE AND DESIGN

Genetic screening in multiple endocrine neoplasia type 2 (MEN 2) has led to specific management guidelines based on genotype-phenotype analysis. However, there is controversy regarding the appropriate age for prophylactic thyroidectomy in families with mutations in codon 804 in exon 14 of the RET proto-oncogene, where medullary thyroid cancer (MTC) may not develop until adulthood. We prospectively studied two MEN 2A families, one with the V804L and the other with the V804M RET mutation, to report our experience of genetic and biochemical screening and prophylactic thyroidectomy. Family 1 is one of the largest MEN 2A families in the literature, where 22 prophylactic thyroidectomies have been performed.

PATIENTS AND RESULTS

C-cell hyperplasia (CCH) was found in 23 out of 25 thyroidectomy specimens from family members of ages 5 years and upwards. MTC was found in 10 out of 18 adults of age 25 years upwards, including the family 2 proband, who was found to have MTC with lymph node metastases at age 28. Phaeochromocytoma was only observed in one patient, but six cases of histologically confirmed hyperparathyroidism were seen in family 1.

CONCLUSION

We suggest that prophylactic thyroidectomy should not be delayed until adulthood in MEN 2A families carrying codon 804 RET mutations, but should be performed when there is CCH, before the development of MTC, as close as possible to age 6 years, which is the age of the youngest reported case of MTC in '804' families.

The peripheral axonal branch of primary sensory neurons readily regenerates after peripheral nerve injury, but the central branch, which courses in the dorsal columns of the spinal cord, does not. However, if a peripheral nerve is transected before a spinal cord injury, sensory neurons that course in the dorsal columns will regenerate, presumably because their intrinsic growth capacity is enhanced by the priming peripheral nerve lesion. As the effective priming lesion is made before the spinal cord injury it would clearly have no clinical utility, and unfortunately, a priming lesion made after a spinal cord injury results in an abortive regenerative response. Here, we show that two priming lesions, one made at the time of a spinal cord injury and a second 1 week after a spinal cord injury, in fact, promote dramatic regeneration, within and beyond the lesion. The first lesion, we hypothesize, enhances intrinsic growth capacity, and the second one sustains it, providing a paradigm for promoting CNS regeneration after injury.

BACKGROUND

Outcomes from this trial's first year data demonstrated significant benefit in heart transplant patients treated with pravastatin in cholesterol levels, survival, rejection with hemodynamic compromise, the development of cardiac allograft vasculopathy, and decreased natural killer cell cytotoxicity. Other heart transplant studies have shown similar benefit. We now report the 10-year follow-up of this study.

METHODS

Ninety-seven heart transplant recipients were randomized to pravastatin (n = 47) or no pravastatin (n = 50) within 2 weeks after surgery both in combination with cyclosporine and corticosteroids. Ten-year outcomes include survival, cholesterol levels, and development of cardiac allograft vasculopathy documented by coronary angiography.

RESULTS

Forty-two percent of the control patients crossed over to pravastatin treatment during the second year of the study, and 81% of the control patients were eventually placed on statin therapy by the 10-year follow-up. The control group had subsequent low and comparable cholesterol levels in Years 2 to 10 of the study compared with the patients originally randomized to pravastatin. Intent-to-treat analysis demonstrated that the pravastatin group compared with control had increased 10-year survival (68% vs 48%, p = 0.026). The 10-year freedom from angiographic cardiac allograft vasculopathy and/or death in the pravastatin group was significantly greater compared with the control group (43% vs 20%, p = 0.009).

CONCLUSION

The 10-year follow-up of this study suggests that the use of pravastatin in heart transplant patients maintains survival benefit and appears to reduce the development of cardiac allograft vasculopathy.

INTRODUCTION

Preservation and restoration of erectile function after radical prostatectomy (RP) for prostate cancer has been extensively studied. However, the influence of RP on the sexual function of female partners is poorly understood.

AIM

The purpose of this retrospective study is to assess sexuality in men who have undergone RP for prostate cancer and their female partners.

METHODS

Men who underwent RP for localized prostate cancer at our institution from 1996 to 2000 were identified and invited to participate in this study with their female partners. Both partners completed a demographic survey. Men completed the International Index of Erectile Function (IIEF) and female partners completed the Female Sexual Function Index (FSFI) and supplemental questions.

MAIN OUTCOME MEASURES

Correlation between IIEF and FSFI domain scores was determined in matched couples using Pearson correlation coefficient. Kappa statistics and Spearman correlation coefficient were calculated for supplemental questions and IIEF domain scores.

RESULTS

Of 1,134 men contacted by letter, 90 (8%) couples completed demographic surveys and both the IIEF/FSFI. Pearson correlation coefficients of IIEF and FSFI domain scores in matched couples demonstrated significant correlation (P0.05) of all IIEF domains with all FSFI domains with the exception of male erectile function and overall sexual function with female sexual desire. There was moderate agreement between partner supplemental questions and IIEF domain scores.

CONCLUSIONS

Response rate was very low. FSFI domain scores correlate with IIEF domain scores, indicating an interrelationship between male and female sexual dysfunction in these couples. Evaluation and treatment of sexual dysfunction after RP should involve both partners.