Ocular syphilis and neurosyphilis in a patient with human immunodeficiency virus infection

A patient who presented with severely decreased bilateral vision was found to have syphilis and neurosyphilis that responded well to a 14-day course of penicillin and prednisone. The patient tested positive for HIV, which can alter the natural course of syphilis, often making the diagnosis and treatment difficult. Conventional therapy for syphilis may not be effective in patients with HIV. Any patient with syphilis who is in a high-risk group should be tested for HIV; conversely, any patient with HIV should be tested for syphilis if signs or suspicions exist.     

Circulating p53 antibodies as early markers of oral cancer: correlation with p53 alterations

p53 aberrations are early events in the pathogenesis of betel- and tobacco-related oral malignancies. Accumulation of p53 protein in oral lesions may elicit a humoral immune response against p53 protein in these patients. p53 antibodies (Abs) were analyzed in 183 sera obtained from patients with premalignant or malignant oral lesions and normal individuals by enzyme-linked immunoassay using recombinant p53 protein as antigen. These results were correlated with accumulation of p53 protein in patients' matched oral tissue specimens. Circulating p53 Abs were observed in 24 of 70 (34%) cancer patients and 15 of 50 (30%) patients with premalignant oral lesions. p53 Abs showed a significant association with increase in tumor size and dedifferentiation of tumors, factors indicative of poor prognosis. Expression of p53 protein was analyzed in 43 matched oral lesions (18 premalignant and 25 malignant cases). All the p53-seropositive patients (7 leukoplakia and 11 squamous cell carcinoma) showed elevated levels of p53 protein in matched oral lesions. However, the total number of patients seropositive for p53 Abs was lesser than that of patients exhibiting p53 protein accumulation in oral lesions. Four of the 63 normal healthy individuals who were heavy consumers of tobacco (smoking/chewing) and betel were found to be positive for p53 Abs. Detection of circulating p53 Abs in patients with premalignant oral lesions suggests that humoral immune response against p53 protein is an early event in oral oncogenesis and may be a surrogate marker for both p53 alteration and preclinical cancer.     

Treponemal specific tests for the serodiagnosis of syphilis. Syphilis and HIV Study Group

OBJECTIVES: To determine the rate of concordance of the Microhemagglutination Assay for Antibodies to T. pallidum (MHA-TP) and the Fluorescent Treponemal Antibody-Absorption test (FTA-ABS) prior to therapy in patients with early stage syphilis and to assess the incidence of and associated risk factors for seroreversion of these treponemal specific tests during the first year after therapy for early syphilis. DESIGN: Multicenter, prospective, cohort treatment study of patients with early syphilis. METHODS: Five hundred twenty-five patients were enrolled in a study to evaluate the response of early syphilis to either benzathine penicillin 2.4 million units intramuscularly once or this therapy plus amoxicillin 2 g and probenecid 500 mg orally both three times daily for 10 days. Serologic and clinical follow-up was conducted at intervals over 1 year. MHA-TP and FTA-ABS tests were performed on serologic specimens from each patient visit. RESULTS: Enrollment specimens showed 5% discordant MHA-TP and FTA-ABS results with 85% of these demonstrating a nonreactive MHA-TP. This occurred most commonly in primary syphilis. In patients who had a 1-year serologic follow-up with FTA-ABS or MHA-TP, seroreversion occurred in 9% and 5% of cases, respectively. No association between HIV-seropositivity and TST seroreversion was demonstrated. CONCLUSION: The MHA-TP may be less sensitive than the FTA-ABS for identifying patients with primary syphilis. Treponemal specific tests may become nonreactive during the first year after therapy for early syphilis.     

Nutritional status of participants in the Giessen Senior Long-Term Study with respect to antioxidant vitamins and selenium

The vast majority of the human experience with viral infections is associated with acute symptoms, such as malaise, fever, chills, rhinitis and diarrhea. With this acute or lytic phase, the immune system mounts a response and eliminates the viral agent while acquiring antibodies to that specific viral subtype. With latent or chronic infections, the viral agent becomes incorporated into the human genome. Viral agents capable of integration into the host's genetic material are particularly dangerous and may commandeer the host's ability to regulate normal cell growth and proliferation. The oncogenic viruses may immortalize the host cell, and facilitate malignant transformation. Cell growth and proliferation may be enhanced by viral interference with tumor suppressor gene function (p53 and pRb). Viruses may act as vectors for mutated proto-oncogenes (oncogenes). Overexpression of these oncogenes in viral-infected cells interferes with normal cell function and allows unregulated cell growth and proliferation, which may lead to malignant transformation and tumour formation. Development of oral neoplasms, both benign and malignant, has been linked to several viruses. Epstein-Barr virus is associated with oral hairy leukoplakia, lymphoproliferative disease, lymphoepithelial carcinoma, B-cell lymphomas, and nasopharyngeal carcinoma. Human herpesvirus-8 has been implicated in all forms of Kaposi's sarcoma, primary effusion lymphomas, multiple myeloma, angioimmunoblastic lymphadenopathy, and Castleman's disease. Human herpesvirus-6 has been detected in lymphoproliferative disease, lymphomas, Hodgkin's disease, and oral squamous cell carcinoma. The role of human papillomavirus in benign (squamous papilloma, focal epithelial hyperplasia, condyloma acuminatum, verruca vulgaris), premalignant (oral epithelial dysplasia), and malignant (squamous cell carcinoma) neoplasms within the oral cavity is well recognized. Herpes simplex virus may participate as a cofactor in oral squamous cell carcinoma development by enhancing activation, amplification, and overexpression of pre-existing oncogenes within neoplastic tissues. Because of the integral role of viruses in malignant transformation of host cells, innovative antiviral therapy may prevent tumour development, involute neoplastic proliferations, or arrest malignant progression.     

Gastric syphilis: polymerase chain reaction detection of treponemal DNA in pseudolymphomatous lesions

Syphilis is an unexpected diagnosis in the stomach. To establish the diagnosis, evidence of Treponema pallidum in the gastric lesion is necessary. However, it is sometimes difficult to prove the presence of the organisms by conventional methods. The authors describe two cases of early gastric syphilis with pseudolymphomatous histology in which T pallidum gene was detected by the polymerase chain reaction (PCR) using paraffin biopsy sections. The gastric lesion of each case endoscopically and histologically simulated that of malignant lymphoma. However, no clonality was proved by immunohistochemistry or PCR gene rearrangement analysis. No spirochetal organisms were detected with certainty by Warthin-Starry silver stain, whereas the organisms were shown by immunofluorescent stain in one patient. A PCR study showed the treponemal DNA in both patients, and its validity was supported by a direct sequencing and a restriction enzyme digestion. Positive results of serological tests for syphilis and regression of the lesions after antisyphilitic treatment were confirmatory of the diagnosis. Gastric syphilis should be considered as a differential diagnosis when an atypical lymphoid infiltrate fails to show monoclonality. The present PCR method would be helpful in showing T pallidum using routinely processed small biopsy specimens as the tissue source.     

Melanoma arising from the mucosal surfaces of the head and neck

Oral mucosal malignant melanoma is a rare disease. We reviewed 30 years of data from a tumor registry and identified 65 patients who had head and neck melanomas. Two thirds (43) of the 65 patients were identified as male, with the mean age in the sixth decade. Of the 65 patients, only 6 had melanoma that arose from the oropharyngeal mucosa. Of the lesions involving the oral mucosa, each lesion manifested itself as a mass or was associated with symptoms of discomfort; only one third (2) of the lesions were pigmented. The clinician must carefully examine the head, neck, and oral cavity, and any pigmented lesion that is not recognized as a specific entity, such as amalgam tattoo, should be biopsied. The more common presentation of amelanotic malignant melanoma requires a high index of suspicion for masses identified in the mouth and requires biopsy for definitive diagnosis. The prognosis for oral mucosal malignant melanoma is poor.     

Gutenberg recycled

The Tuskegee Study, an observational study of over 400 sharecroppers with untreated syphilis, was conducted by the U.S. Public Health Service to document the course of the disease in blacks, and racial differences in the clinical manifestations of syphilis. The men were not told they had syphilis, not given counseling on avoiding spread of the disease, and not given treatment throughout the course of the study. The study became the longest (1932-1972) nontherapeutic experiment on humans in the history of medicine, and has come to represent not only the exploitation of blacks in medical history, but the potential for exploitation of any population that may be vulnerable because of race, ethnicity, gender, disability, age or social class. It is important for physicians who will be caring for an increasingly diverse nation to understand the lasting implications of this study for their patients, but the effects of the Tuskegee Syphilis Study are demonstrated most strikingly by unsuccessful attempts at improving representation of minority patients in clinical trials.     

Human immunodeficiency virus seropositivity in adolescents with syphilis

OBJECTIVE: The purpose of this study was to assess the relationship between syphilis and human immunodeficiency virus (HIV) infection among inner-city, minority group adolescents. METHODS: From August 1989 through June 1990, serum from all positive serologic tests for syphilis, obtained from patients attending a comprehensive adolescent health center in an acquired immunodeficiency syndrome epicenter and its two school-based clinics, were frozen without patient identifiers and were subsequently screened for HIV by enzyme-linked immunosorbent assay with confirmatory Western blot for positives. In addition, a retrospective chart review was performed for all patients with a positive serologic test for syphilis during the study period. RESULTS: Of the 59 specimens with a positive syphilis serologic test, 9 (15.3%) were HIV seropositive. Of the patients with syphilis, 57.4% were black and 42.6% were Hispanic; 16.4% were male (mean age 18.1) and 83.6% were female (mean age 17.8). Only 1 subject (female) was an injection drug user; 4 of the male subjects self-identified as having had sex with other males. Of the subjects, 27.8% had primary, 19.7% had secondary, and 52.5% had latent syphilis at the time of diagnosis. A prior or concurrent sexually transmitted disease was present in 90% of the males and 80% of the females; gonorrhea was the most prevalent sexually transmitted disease in the males (89%) and chlamydia was most prevalent in the females (35%). A history of chancroid and/or herpes was present in 16.4% of the subjects. CONCLUSIONS: It is concluded that the diagnosis of syphilis in an adolescent is a risk factor for HIV infection. All sexually active adolescents should be routinely screened for syphilis, regardless of sexual practices. Those with syphilis should be specifically counseled about their increased risk for HIV infection and the importance of consistent condom use, and they should be referred for formal HIV pretest counseling.     

Assessing the patient at risk for oral squamous cell carcinoma

Patients and health care workers require continuing education to promote knowledge of the signs, symptoms, and risk factors for oral cancer. This paper reviews the literature assessing diagnostic tools that are currently available or being developed, in order to assist in the biopsy site selection and subsequent diagnosis of patients at risk for oral cancer. There is a general consensus that oral examination of patients at risk for oral squamous cell carcinoma (SCC) should be conducted on a routine basis. However, there can be false-positive and false-negative findings. Toluidine blue has been shown to be useful as an adjunct to the clinical examination when used by experienced clinicians. Exfoliative cytology is not currently used as a routine measure for the evaluation of lesions of the oral mucosa, but further development and the application of biologic markers to cytologic specimens may increase its value. Fluorescent imaging of malignant lesions of the oral mucosa has been shown to be sensitive and specific in animal models but thus far has been reported in only one human trial. The sensitivity and specificity of these techniques when used by general practitioners need to be assessed. Further, none of the above procedures has yet been shown to be a cost-effective public health measure in screening for oral cancer.     

Protective sensation of the plantar aspect of the foot

For decades pregnancy has been regarded as an unfavourable prognostic factor in women with malignant melanoma and for many patients termination of pregnancy was recommended. Likewise, it was suspected that pregnancy during the first few years after diagnosis of the tumor would impair the prognosis and, therefore, a contraindication was established. An analysis of the data of the Central Malignant Melanoma Registry of the German Dermatological Society revealed that 1% of female melanoma patients were pregnant and 40.5% were found to be in premenopausal status. In several recent studies survival rates of melanoma patients who were pregnant and those who became pregnant after diagnosis were compared to the rates in women without pregnancies. No significant differences were found. In addition, the use of oral contraceptives and menopausal estrogens, which were formerly thought to be related to an elevated risk of developing melanoma, was shown not to affect the risk and natural course of malignant melanoma. In conclusion, the recent results of extensive investigations no longer substantiate recommendations for abortion in pregnant melanoma patients. The use of oral contraceptives and menopausal estrogens is likewise no longer contraindicated in melanoma patients. A waiting period before having children may be recommended in the first 2-3 years after diagnosis, as this is the period with the highest probability of relapse, and one can be more certain that the course will be favourable.     

Malignant hyperthermia: attempt at an early diagnosis by means of determination of creatine phosphokinase (CPK) and its isoenzymes

Creatinphosphokinase (CPK) was elevated in sera of patients with malignant hyperthermia and in sera of some of their relatives. Only the MM-isoenzyme (but not the MB- or the BB-isoenzyme) could be detected by paperchromatographic analysis. In some of the patients elevation of muscle aldolase was also observed. Thus, the appearance of the BB-isoenzyme in sera of patients with malignant hyperthermia, as described by another group of investigators, was not confirmed. No specific screening method exists as yet to detect patients with a high risk of developing this often lethal reaction to anesthesia. However, in patients without muscle disease or trauma and without prior i.m. injections, myocardial infarction or major physical strain, elevation of CPK in serum should be interpreted as meaning that malignant hyperthermia may develop during anesthesia. The pathophysiology of malignant hyperthermia is discussed.     

Emergency department screening for syphilis in pregnant women without prenatal care

STUDY OBJECTIVE: To determine if there is a high seroprevalence of syphilis in pregnant women without prenatal care presenting to an urban emergency department. DESIGN: Prospective, nonblinded sampling of pregnant women without prenatal care with a comparison group of pregnant women with prenatal care from the obstetrics clinic. Patients in the ED setting were asked about such associated risk factors as previous syphilis and drug use. SETTING: Urban ED. TYPE OF PARTICIPANTS: Pregnant women without prenatal care. INTERVENTION: Patients were screened for syphilis using the automated reagin test. Reactive automated reagin tests were confirmed by the fluorescent treponemal antibody absorption. In addition, 44 patients with nonreactive automated reagin tests had confirmatory tests done. New cases were verified by the state health department. MEASUREMENTS AND MAIN RESULTS: Seventy-two patients were included in the study. The average age was 25 years. Eight patients (11.1%) were diagnosed with previously undetected syphilis. Four patients (5.6%) had previously treated syphilis. The laboratory cost of screening was $248 per new case of syphilis detected. The study group was compared with 118 patients matched for age and race who presented to the obstetrics clinic for routine prenatal care. Two new cases of syphilis were discovered in the clinic population (1.7%). CONCLUSION: A high rate of syphilis infection was detected in this inner-city ED population presenting without prenatal care. This was higher than that found in the patients presenting for obstetrics care in the clinic. Patients can be screened effectively in the ED.     

Preliminary evidence for an association of Epstein-Barr virus with pre-ulcerative oral lesions in patients with recurrent aphthous ulcers or Beh?et's disease

In this study we used the polymerase chain reaction (PCR), slot blot and Southern blot hybridization, direct sequencing and in situ hybridization (ISH) to show the possible presence of EBV-DNA in pre-ulcerative oral aphthous lesions of patients with recurrent aphthous ulcers (RAU) or Beh?et's disease (BD). For this purpose, formalin-fixed biopsy specimens were obtained from 13 pre-ulcerative oral aphthous lesions of nine RAU and four BD patients. Five specimens of normal oral mucosa (NOM) from five normal control subjects and 10 specimens of oral erosive or ulcerative lesions from 10 patients with erosive lichen planus (ELP) were also included. EBV-DNA was detected by PCR in 5 of the 13 (38.5%) pre-ulcerative oral aphthous lesions, two from RAU patients and three from BD patients. However, no EBV-DNA was demonstrated in five NOM specimens from normal control subjects and in 10 specimens of oral lesions from ELP patients. EBV-DNA was also demonstrated in patients' peripheral blood lymphocytes and/or plasma, suggesting that the lymphocytes may be the reservoir of latent EBV infection and there is EBV shedding in the plasma. EBV-DNA was detected by ISH in only one PCR-positive case; the reaction product was found to deposit on the nuclei of some of the epithelial cells and lymphocytes. By immunohistochemistry, expression of Epstein-Barr nuclear antigen and EBV/C3d receptors was also noted in some of the epithelial cells and lymphocytes in this ISH-positive case. Therefore, we suggest that the epithelial cells of pre-ulcerative oral aphthous lesions may be infected by EBV through EBV-infected lymphocytes; also, the cytotoxic T lymphocyte-induced lysis of the EBV-infected epithelial cells, but not the virus-induced cytolysis, may be the main mechanism causing oral ulcer formation. Our data provide preliminary evidence for an association of EBV with pre-ulcerative oral aphthous lesions in RAU and BD patients.     

Relapsing syphilis

Although penicillin still remains highly effective for syphilis, concerns have been raised that current regimens may be inadequate for the treatment of early syphilis. We report the failure of benzathine penicillin in the treatment of secondary syphilis. Extensive tracing of sexual contact history failed to identify sources of possible reinfection; therefore, we believe that this case represents a treatment failure and an ensuing relapse of secondary syphilis.     

Regulation of megakaryocytopoiesis and platelet production: lessons from animal models

We showed differential expression of HSP70 during oral tumorigenesis. The precise functional role of HSP70 overexpression in the pathogenesis of betel and tobacco related oral cancer remains to be determined. To evaluate the utility of HSP70 as an indicator of the biological stress experienced by tumour cells or the malignant potential of oral epithelial lesions and predicting clinical outcome, its expression was assessed in different stages of oral carcinogenesis by immunohistochemical analysis and correlated with clinicopathological parameters. Overexpression of HSP70 protein was observed in 38 of 64 (59%) dysplastic lesions and 92 of 125 (74%) oral squamous cell carcinomas (SCCs) which included 76 of 105 cases (72%) of primary oral SCCs and 16 of 20 (80%) of recurrent oral SCCs. A significant correlation of HSP70 expression was observed with severity of dysplasia (P = 0.0006767), poor histological differentiation of primary tumours (P = 0.0184348), increase primary tumour size (P = 0.0221103) and consumption of betel and tobacco (P < 0.01). Follow-up studies showed that in patients with premalignant lesions the median transition time (premalignancy to malignancy) was significantly shorter in HSP70 overexpressing cases than those showing basal level of HSP70 (P = 0.012). Oral cancer patients with elevated levels of HSP70 showed decreased median disease-free survival time (no recurrence/metastasis) than those showing basal HSP70 immunoreactivity (P = 0.0246). The results suggest that HSP70 expression may not be a mere marker of biological stress but may also be implicated in the pathogenesis of oral cancer.     

A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood

Recent studies have indicated that the proliferation of malignant gliomas is in part dependent on excessive activation of protein kinase C (PKC)-mediated pathways. Conversely, inhibiting PKC may provide a novel approach for blocking glioma growth. The antiestrogen tamoxifen, a moderately potent PKC inhibitor, has been shown in vitro to block the proliferation of malignant glioma cell lines at concentrations several-fold higher than those typically attained during the treatment of breast cancer; such serum concentrations may be achieved with doses > 40 mg/m2 b.i.d. The safety and efficacy of these high doses for producing disease control in patients with malignant gliomas has recently been noted anecdotally, although a rigorous study of this agent has been lacking. To address this issue, we examined the safety and efficacy of high-dose tamoxifen in a series of children with malignant gliomas that had progressed after conventional therapy. An initial group was treated with 60 mg/m2 p.o. b.i.d. and a second group with 100 mg/m2 b.i.d. Steady-state serum tamoxifen and metabolite levels were measured in most patients. Toxicity with the regimen was minimal; two patients treated at the higher dose required reduction to the lower dose because of asymptomatic prolongation of the QT interval on an electrocardiogram. Although none of the patients exhibited clear-cut tumor regression, 4 of 14 patients had stabilization of previously progressive disease for at least 3 months; the longest survivor lived for 17 months after beginning tamoxifen. The moderate efficacy of this agent in otherwise end-stage disease coupled with its low toxicity and the relative ease of oral administration provides a rationale for proceeding with larger studies of this agent in patients with malignant gliomas, possibly as a means for potentiating the effects of conventional chemotherapeutic agents, which to date have shown limited efficacy in the treatment of these tumors.     

Auricular fibrillation, systemic embolism and anticoagulant treatment

The risk of arterial embolism, specially cerebral, in patients with mitral stenosis associated atrial fibrillation is seventeen fold greater than that of the general population and five fold greater than that of non rheumatic atrial fibrillation. The usefulness of oral anticoagulant therapy in patients with atrial fibrillation and mitral stenosis is clear. In patients with non rheumatic atrial fibrillation, the controversy about its usefulness has been cleared with five recent reports showing a significant benefit or oral anticoagulation. We believe that these results may be applied to the routine management of these patients provided an adequate patient selection, consideration of contraindications and the use of a low anticoagulation range. Aspirin effectiveness in these patients is unsettled. One study showed benefits of 375 mg/day in patients younger than 75 years. The embolic risk in patients with atrial fibrillation must be stratified. High risk patients require the use of oral anticoagulation with an INR range between 3 and 4.5; those with medium risk require an INR between 2 and 3 and in some, aspirin use may be an alternative. When electrical cardioversion is indicated, oral anticoagulation must be used when atrial fibrillation has lasted for more than two days. In these cases, it is advisable to postpone cardioversion for three weeks after oral coagulation has started and to maintain this treatment for 3 or 4 additional weeks after cardioversion.     

False-negative syphilis screening due to change in temperature

BACKGROUND AND OBJECTIVES: Inaccurate test results for syphilis may cause an individual to experience serious effects. GOAL OF THE STUDY: Investigate potential sources of error and test limitations causing false-negative reactions. STUDY DESIGN: In 5 months, two laboratories screened 2,232 patients for syphilis by the Rapid Plasma Reagin (RPR) test. RESULTS: The hospital laboratory reported 5.3% (64/1,210) of patients' test as reactive on initial screening, and the research laboratory found 6.4% (78/1,210) reactive. Fourteen reactive patients were incorrectly reported negative by the hospital laboratory, as confirmed by both laboratories. A refrigerated centrifuge in the hospital laboratory possibly caused sera to be cooled before testing, producing false-negative results. When its temperature was adjusted from 4 degrees C to 27 degrees C, an additional 1,022 samples tested were consistent between the two laboratories. CONCLUSION: Cold temperature produces false-negative reactions for syphilis screenings in patients' samples with titers < 1:4 dilution. Patients' samples with titers > or = 1:16 dilution were not affected. According to this study, incorrect temperatures for test sera can alter testing outcomes. Therefore, test manufacturer's directions must be strictly followed.     

General paralysis of the insane and AIDS in old age psychiatry: epidemiology, clinical diagnosis, serology and ethics--the way forward

While the incidence of general paralysis of the insane (GPI) has declined, AIDS (acquired immune deficiency syndrome) has emerged as a new illness. Today, in England and Wales, as many elderly people die from AIDS as from neurosyphilis, although both diagnoses are rare in this age group. Both are serious medical conditions with psychiatric manifestations. For both, serological tests may identify the disease, and treatment may be of benefit, but there is considerable social stigma attached to the diagnoses. Ethical guidelines for serological testing for HIV (human immunodeficiency virus) have been available for over a decade. In view of the similarities between the diseases, it may be unethical to test patients for syphilis routinely. Epidemiology, risk factors, neurological and neuropsychiatric features and ethics must be considered before testing for both syphilis and HIV.