Wilson's disease in pregnancy: five successful consecutive pregnancies of the same woman

Wilson's disease is an autosomal recessive disorder of copper metabolism characterized mainly by liver cirrhosis and neurological disorders. Appropriate treatment with chelating agents allows normal fertility function. We report five consecutive successful pregnancies of the same woman, treated in the high-risk unit at our medical center. The management dilemmas and treatment options are discussed.     

Genetic studies in Alzheimer's disease

Alzheimer's disease (AD), the most common cause of dementia in aged populations, is believed to be caused by both environmental factors and genetic variations. Extensive linkage and association studies have established that a broad range of loci are associated with AD, including both causative and susceptibility (risk factor) genes. So far, at least three genes, APP, PS1, and PS2, have been identified as causative genes. Mutations in these genes have been found to cause mainly early-onset AD. On the other hand, APOE has been identified to be the most common high genetic risk factor for late-onset AD. Polymorphisms in the coding region, intron, and promoter region of certain genes constitute another kind of genetic variation associated with AD. A number of other genes or loci have been reported to have linkage with AD, but many show only a weak linkage or the results are not well reproduced. Currently, the measurable genetic associations account for about 50% of the population risk for AD. It is believed that more new loci will be found to associate with AD, either as causative genes or genetic risk factors, and that eventually the understanding of genetic factors in the pathogenesis of AD will be important for our efforts to cure this illness.     

Analysis of treatment results for base of tongue cancer

OBJECTIVE: The study reported the results of treatment for base of tongue cancer with five different treatment modalities with long-term follow-up. STUDY DESIGN: This was a retrospective study of 262 patients with base of tongue cancer treated in the Departments of Otolaryngology-Head and Neck Surgery and Radiation Therapy at Washington University School of Medicine (St. Louis, MO) from July 1955 to January 1998. METHODS: The study population included previously untreated patients with biopsy-proven squamous cell carcinoma of the base of tongue who were treated with curative intent by one of five modalities and were all eligible for 5-year follow-up. The treatment modalities included local resection alone, composite resection alone, radiation therapy alone, local resection with radiation therapy, and composite resection with radiation therapy. Multiple diagnostic, treatment, and follow-up parameters were studied using standard statistical analysis to determine statistical significance. RESULTS: The overall 5-year disease-specific survival (DSS) was 49.6% with death due to tumor in 50.4%. The 5-year cumulative disease-specific survival probability (CDSS) was 0.526 (Kaplan-Meier) with a mean of 7.8 years and a median of 5.6 years. Patients with early disease had significantly improved DSS compared with patients with more advanced disease (stages I and II; TN stages T1N0, T2N0, and T2N1; and T stages T1 and T2.). Patients with N0 had better DSS than patients with positive lymph nodes (P =.010). The DSS for all stages by treatment modality included local resection (70.0%), composite resection (47.6%), radiation therapy (40.4%), local resection and radiation therapy (50.0%), and composite resection with radiation therapy (51.5%). Overall and within the stages there was no significant difference in either DSS or CDSS by treatment modality. Local-regional recurrence occurred in 26% of patients, and overall salvage was 10.5%. Patients with clear resection margins did better than patients with close or involved margins (DSS and CDSS). Patients treated with radiation therapy alone had improved capacity to swallow (P =.001), speak (P =.01), and work (P =.001) compared with patients treated with the other modalities. CONCLUSIONS: Cancer of the base of tongue is a lethal disease, and its treatment results in significant disability. No treatment produced a significantly improved survival advantage. Focus on improving local-regional control might improve overall survival. All treatment modalities were associated with major treatment-related complications. Radiation alone produced significantly improved post-treatment function and quality of life compared with the other modalities. Because of the recurrence rates at the primary and neck sites and the high rates of development of distant metastasis and second primary cancers, patients should be monitored for a minimum of at least 4 years.     

Immunization of HIV-infected children with varicella vaccine

OBJECTIVE: To determine the safety and immunogenicity of varicella vaccine in children with human immunodeficiency virus (HIV) infection. Children (n = 41) who were mildly affected by HIV (Centers for Disease Control and Prevention stage N1 or A1) and had no history or serum antibody indicative of prior varicella infection were immunized with two doses of live attenuated varicella vaccine. RESULTS: A minority of the vaccine recipients had mild local or systemic reactions. Vaccination had no effect on the clinical stage of HIV or the HIV RNA plasma load. CD4 cell percentage and CD4 cell count were marginally decreased at week 4 after the first vaccination; this effect was no longer present at week 8 after vaccination. Two months after the second dose of vaccine, 60% of vaccine recipients had anti-varicella antibody in their serum, and 83% had a positive lymphocyte proliferation assay response to varicella antigen. CONCLUSION: On the basis of its safety and immunogenicity, varicella vaccine should be considered in the childhood vaccines given to mildly affected HIV-infected children.     

Prevalence and risk factors for bloodborne exposure and infection in correctional healthcare workers.

OBJECTIVE: To determine the prevalence and risk factors for bloodborne exposure and infection in correctional healthcare workers (CHCWs).Design. Cross-sectional risk assessment study with a confidential questionnaire and serological testing performed during 1999-2000. SETTING: Correctional systems in 3 states. RESULTS: Among 310 participating CHCWs, the rate of percutaneous injury (PI) was 32 PIs per 100 person-years overall and 42 PIs per 100 person-years for CHCWs with clinical job duties. Underreporting was common, with only 25 (49%) of 51 PIs formally reported to the administration. Independent risk factors for experiencing PI included being age 45 or older (adjusted odds ratio [aOR], 2.41 [95% confidence interval (CI), 1.31-4.46]) and having job duties that involved needle contact (aOR, 3.70 [95% CI, 1.28-10.63]) or blood contact (aOR, 5.05 [95% CI, 1.45-17.54]). Overall, 222 CHCWs (72%) reported having received a primary hepatitis B vaccination series; of these, 150 (68%) tested positive for anti-hepatitis B surface antigen, with negative results significantly associated with receipt of last dose more than 5 years previously. Serologic markers of hepatitis B virus infection were identified in 31 individuals (10%), and the prevalence of hepatitis C virus infection was 2% (n=7). The high hepatitis B vaccination rate limited the ability to identify risk factors for infection, but hepatitis C virus infection correlated with community risk factors only. CONCLUSION: Although the wide coverage with hepatitis B vaccination and the decreasing rate of hepatitis C virus infection in the general population are encouraging, the high rate of exposure in CHCWs and the lack of exposure documentation are concerns. Continued efforts to develop interventions to reduce exposures and encourage reporting should be implemented and evaluated in correctional healthcare settings. These interventions should address infection control barriers unique to the correctional setting.     

Progesterone levels in cesarean and normal delivered term placentas

Background  

One of the most important hormones synthesized by the placenta during pregnancy is progesterone. The regulating mechanisms of progesterone synthesis and the mechanism responsible for the spontaneous onset of labor in women are still not fully understood. Progesterone is thought to have been involved in human parturition. The objective of this study was to compare the levels of progesterone in the human placentas, at the end of the gestation (37–41 weeks) in vaginal versus cesarean deliveries, and to evaluate the pattern of progesterone accumulation, instantly following its synthesis by the human placenta at the end of the pregnancy.     

Detection of the 5-HT1A receptor and 5-HT1A receptor mRNA in the rat bowel and pancreas: Comparison with 5-HT1Preceptors

We tested the hypothesis that the rat bowel and pancreas contain 5-HT_1A receptors. ₃H-8-hydroxy-2-(di-n-propylamino) tetralin (₃H-8-OH-DPAT) was used as a radioligand. Binding of ₃H-8-OH-DPAT to membranes derived from the myenteric plexus and the pancreas was investigated by rapid filtration. Alternatively, radioautography was employed to locate ₃H-8-OH-DPAT binding sites in frozen sections of unfixed bowel or pancreas. An excess of 5-HT (10 μM) was used to define nonspecific binding. Saturable, high affinity binding of ₃H-8-OH-DPAT to enteric (K_d= 2.8 ± 1.1 nM; B_max =83.8 ± 4.3 fmol/mgproteim) and pancreatic (K_d = 6.6 ± 1.3 nM; B_max = 44 ± 2.2 fmol/mg protein) membranes was found. The binding of ₃H-8-OH-DPAT to enteric and pancreatic membranes was inhibited by 8-OH-DPAT, NAN-190, and spiperone. In contrast, the binding of ₃H-8-OH-DPAT to enteric and pancreatic membranes was not inhibited by 5-carboxyamidotryptamine, or by avariety of compounds known to bind to other subtypes of 5-HT receptor. Digoxigenin-labeled oligonucleotides were found to detect mRNA encoding the 5-HT_1A receptor in a subset of neurons in myenteric and submucosal ganglia. In contrast, 5-HT_1A mRNA was not found in the pancreas. Radioautography revealed that the highest density of ₃H-8-OH-DPAT binding sites was found in the stomach. These sites were especially numerous in the lamina propria adjacent to gastric glands, and in myenteric ganglia. Pancreatic 5-HT_1Areceptors were located on nerves, lymphoid tissue (especially the capsule of nodes), and on cells scattered in the pancreatic parenchyma. The concentration of ₃H-8-OH-DPAT binding sites in the rat bowel and pancreas was less than that of ₃H-5-HT binding sites; however, the distribution of ₃H-8-OH-DPAT binding sites was similar to that of sites that bind ₃H-5-HT. It is concluded that the rat gut and its extension in the pancreas contains 5-HT_1A receptors. Many, if not all, of the nerve cells and processes that express 5-HT_1A receptors express 5-HT_1p receptors as well. The function of these receptors in the physiology of the entero-pancreatic innervation remains to be determined. © 1993 Wiley-Liss, Inc.     

The impact of surgical margin status and use of an interstitial implant on T1,T2 oral tongue cancers after surgery

In patients with T1, T2 oral tongue carcinoma treated with surgical resection, postoperative radiation therapy (RT) is required especially when surgical margins contain tumors. Irradiation techniques include external beam, interstitial implants, or a combination of the two modalities. We investigated whether positive surgical margin remains a poor prognostic factor after radiation therapy, and the contribution of interstitial implants to disease control.

Between 1972 and 1989, 55 patients were treated postoperatively at the Mallinckrodt Institute of Radiology for T1, T2 squamous cell carcinomas of the oral tongue. Surgeries included 26 wide excisions or excisional biopsies and 29 composite resections or hemiglossectomies. Thirty-nine patients received external radiation therapy alone and 16 patients had an interstitial implant (ISI) as part of the treatment. The minimum follow-up is 4 years.

At 2 and 5 years, the overall survivals for all patients were 82 and 68%. The disease-free survivals (DFS) were 82 and 70%, respectively. There was no significant difference in the pattern of failure and DFS when stratified by the status of surgical margins and the type of the surgical procedure. Local control was achieved in 15 of 18 patients when surgical margins were involved by tumor and in 29 of 37 patients without tumor involving margins (p = 0.05). Ten of 18 (56%) patients with tumor involving resection margins were treated with ISI, whereas only 3 or 33 (9%) of those with negative margins received ISI. Local control was achieved in 32 of 39 patients treated with external beam RT alone, and 13 of 16 patients who received interstitial implant (p = 0.05). Four patients treated with ISI developed persistent soft tissue ulceration and mandibular bone exposure.

Postoperative radiation therapy converted the ominous outcome of patients with tumor involving surgical margins. Patients with positive surgical margins were often selected to be treated with interstitial implants. We found that the local control was as good as in those with a more favorable pathology (negative margins) and treated with external RT alone. Further investigation is needed to optimize the implant treatment to minimize the complications.     

Natural killer cell activity in post-necrotic cirrhotic patients as related to hepatitis-B virus infection and plasma zinc levels

In view of the suggested physiological role of natural killer (NK) cells in immunosurveillance and defence against viral infections, we have investigated the relationship between hepatitis B virus (HBV) infection and NK activity against K-562 cells in patients with post-necrotic cirrhosis. Overall, the NK activity in cirrhotic patients did not differ from age- and sex-matched controls. However, cirrhotic males with evidence of HBV infection with or without HBs antigenemia tend to have lower NK activity than controls. Cirrhotic males without evidence of HBV infection do not differ from controls. Such a trend was not observed in the female cirrhotic patients examined. In addition significantly reduced NK activity was observed in cirrhotic patients with low plasma zinc levels. This relationship is of interest because of the known association between zinc deficiency and various immunodeficiencies.