A Multicenter Retrospective Evaluation of Specialized Laboratory Investigations in the Workup of Pediatric Patients With New-Onset Supraventricular Tachycardia.

INTRODUCTION: Specialized laboratory evaluation of supraventricular tachycardia in children may occur, but the utility is unknown. The study objectives are to assess the type, frequency, and results of specialized laboratory testing performed in pediatric patients presenting with new-onset supraventricular tachycardia. We hypothesized that when specialized laboratory testing occurs (particularly for cardiac failure, toxicologic, inflammatory, and thyroid diseases), the results are generally within normal limits. METHODS: This is a retrospective descriptive study using an electronic health record database (TriNetX, Inc). We collected and evaluated the following data of subjects aged younger than 18 years with a first-time supraventricular tachycardia diagnosis: demographics, diagnostic codes, deaths, and laboratory codes/results (natriuretic peptide B, natriuretic peptide B prohormone N-terminal, troponin I, toxicology testing, inflammatory markers, and thyroid studies). RESULTS: A total of 621 subjects (524 [84.4%] without laboratory testing, 97 [15.6%] with laboratory testing) were included. Thyroid studies (65 [10.5%]) were the most frequent laboratory study performed followed by cardiovascular specific studies (35 [5.6%]), inflammatory markers (21 [3.4%]), and toxicology tests (10 [1.6%]) (P = .002). Obtained laboratory testing was more frequent with older subjects, females, and need for emergency, hospital, and critical care services. DISCUSSION: Cardiac-specific and noncardiac laboratory testing is frequently ordered for pediatric patients who present with supraventricular tachycardia. Thyroid studies were the most common laboratory testing ordered, but abnormal results only occurred in less than a quarter of subjects. These findings may highlight a quality improvement opportunity for emergency nurses and practitioners in the practice of obtaining laboratory tests to better reflect high-value evidence-based care for this vulnerable population.

Measuring the palpable pulsatility length as a physical examination test in defining the severity of inflow stenosis for hemodialysis fistulas.

BACKGROUND: Pulsatility is an important property of hemodialysis arteriovenous fistulas (AVF) and can be perceived by the fingers as a gradual decrease in strength downstream from the anastomosis along the main trunk of the fistula. The distance from the point at which the pulse becomes imperceptible to the anastomosis is termed the palpable pulsatility length (PPL); we considered this length may play a role in assessing the severity of inflow stenosis for hemodialysis fistulas. METHODS: This study was performed by retrospective analysis of routinely collected data. Physical examinations and fistula measurements were performed in a selected population of 76 hemodialysis patients with mature fistulas during half a year. Fistula measurements included the PPL before and after treatment and the distance between the anastomosis and the arterial cannulation site (aPump length). The aPump index (API) was calculated by dividing the PPL by the aPump length. Angiograms were reviewed to determine the location and severity of stenosis. PPL and API were used to detect the critical inflow stenosis, which indicates severe inflow stenosis of an AVF. RESULTS: Receiver operating characteristic analysis showed that the area under the curve was 0.895 for API and 0.878 for PPL. A cutoff value of API < 1.29 and PPL < 11.0 cm were selected to detect the critical inflow stenosis. The sensitivity was 96.0% versus 80.0% and specificity was 84.31% versus 84.31% for API and PPL, respectively. CONCLUSIONS: PPL and API are useful tools in defining the severity of pure inflow stenosis for mature AVFs in the hands of trained examiners with high sensitivity and specificity.

The Difficulty Detecting Tuberculosis in a Child with Post-COVID-19 and Cerebral Palsy.

When hypostatic pneumonia is present at the same time as COVID-19 pneumonia, the clinical course is almost always prolonged (prolonged-COVID-19) due to persistent inflammation, long-term anti-inflammatory syndrome, followed by immune exhaustion, i.e., by immunosuppression and catabolic syndrome. In the immunosuppression phase, viral reactivation can be accompanied by a secondary infection, which, in this case, is pulmonary tuberculosis. Pulmonary tuberculosis in post-COVID-19 patients and in patients with spastic quadriplegic cerebral palsy does not have a typical clinical course nor laboratory, radiological, immunological, microbiological, or fiberbronchoscopic pathohistological confirmation. Due to this, the treatment of pulmonary tuberculosis was not carried out on time, postponed after the unsuccessful treatment of sepsis, post-COVID-19, and other accompanying viral (adenovirus, RSV) and bacterial (streptococcus viridans) infections. The treatment of pulmonary tuberculosis was possible only "ex juvantibus" (trial) post-COVID-19. It becomes imperative to search for a new, more precise and reliable diagnostic test for the detection of tuberculosis bacillus.

Examining the Dominant Presence of Brain Grey Matter in Autism During Functional Magnetic Resonance Imaging.

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with symptoms appearing from early childhood. Behavioral modifications, special education, and medicines are used to treat ASD; however, the effectiveness of the treatments depends on early diagnosis of the disorder. The primary approach in diagnosing ASD is based on clinical interviews and valid scales. Still, methods based on brain imaging could also be possible diagnostic biomarkers for ASD. Methods: To identify the amount of information the functional magnetic resonance imaging (fMRI) reveals on ASD, we reviewed 292 task-based fMRI studies on ASD individuals. This study is part of a systematic review with the registration number CRD42017070975. Results: We observed that face perception, language, attention, and social processing tasks were mainly studied in ASD. In addition, 73 brain regions, nearly 83% of brain grey matter, showed an altered activation between the ASD and normal individuals during these four tasks, either in a lower or a higher activation. Conclusion: Using imaging methods, such as fMRI, to diagnose and predict ASD is a great objective; research similar to the present study could be the initial step.

HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women.

A crucial requirement in the rational design of a prophylactic vaccine against the human immunodeficiency virus (HIV) is to establish whether or not protective immunity can occur following natural infection. The immune response to HIV infection is characterized by very vigorous HIV-specific cytotoxic T-lymphocyte (CTL) activity. We have identified four HIV-1 and HIV-2 cross-reactive peptide epitopes, presented to CTL from HIV-infected Gambians by HLA-B35 (the most common Gambian class I HLA molecule). These peptides were used to elicit HIV-specific CTLs from three out of six repeatedly exposed but HIV-seronegative female prostitutes with HLA-B35. These women remain seronegative with no evidence of HIV infection by polymerase chain reaction or viral culture. Their CTL activity may represent protective immunity against HIV infection.

PIP: A crucial requirement in the rational design of a prophylactic vaccine against HIV is to establish whether or not protective immunity can occur following natural infection. The immune response to HIV infection is characterized by very vigorous HIV-specific cytotoxic T-lymphocyte (CTL) activity. Four HIV-1 and HIV-2 cross-reactive peptide epitopes were identified, presented to CTL from HIV-infected Gambian women by HLA-B35 (the most common Gambian class 1 HLA molecule). The study population consisted of 20 women: 14 had been prostitutes for more than 5 years and reported little condom usage and 6 were long-term sexual partners of HIV-infected men. Peptide-stimulated cultures were also set up from 8 known seropositive donors with HLA-B35 or B53, and from a control group of volunteers at low-risk of HIV infection with HLA-B35 (12 Gambian and 7 European) and 2 Gambians with HLA-B53. Specific CTL activity against one or more peptides was repeatedly detected after 10-14 days in the peptide-stimulated cultures from 3 of the 6 high-risk seronegative women with HLA-B35, but not in their three counterparts with HLA-B53 nor in any of the low-risk volunteers. The strongest responses were generated toward the HIV-1 pol peptide, which lies close to the active site of reverse transcriptase, and to the nef peptide, which is conserved between HIV-1 and -2. HIV-specific CTL in seronegative subjects could potentially be a response to acute HIV infection, before the development of antibodies, but the women were still seronegative and virus-culture negative 3 months after the CTL were first detected, making recent infection extremely unlikely. These women remain seronegative with no evidence of HIV infection by polymerase chain reaction or viral culture. Their CTL activity may represent protective immunity against HIV infection.

A role for a new herpes virus (KSHV) in different forms of Kaposi's sarcoma.

Kaposi's sarcoma (KS) is a previously rare, tumour-like lesion of controversial biological nature. KS has since the early 1980s become frequent in patients with AIDS, particularly in homosexuals. KS is also endemic in Central Africa predominantly in otherwise healthy men but also in women and children. Recently, evidence for the presence of novel, herpes virus DNA sequences in more than 90% of AIDS Kaposi lesions (AKS) was presented. This DNA was identified using representational difference analysis (RDA) generating short, unique sequences with variable homology to several herpes virus, but no intact virus was recovered. If these DNA-sequences are also present in other, non-HIV-associated forms of Kaposi's sarcoma this would strongly suggest a specific, aetiopathological involvement of this putative new herpes virus in the pathogenesis of Kaposi's sarcoma, rather than a contamination of yet another opportunistic virus in immunosuppressed AIDS patients.

PIP: Samples were examined by polymerase chain reaction (PCR) for the presence of the putative Kaposi's sarcoma herpes virus (KSHV). KS DNA from HIV-negative, African, endemic (EKS) samples, and epidemic HIV-positive KS (AKS), and sporadic KS (SKS) samples were tested from Tanzania and Sweden. All of the HIV KS (18 African EKS and 4 Swedish SKS) as well as the HIV-positive AIDS-related KS (16 African and 7 Swedish AKS) biopsies were shown to contain the previously described DNA sequences. KS lesions from children, females, and males in various tissues were analyzed including skin, lymph nodes, gut and oral mucosa. All forms of KS showed a single PCR product of the expected size (233 base pairs). To exclude amplification of other types of herpes virus, virus preparations of Epstein-Barr virus (EBV), herpes simplex virus, cytomegalovirus, vesicular stomatitis, and human herpes virus type 6 (HHV6) were assayed, again by PCR, using the KSHV primers. No PCR products were obtained with any of these virus strains. However, most HIV-positive and HIV-negative KS DNA samples also contained either EBV and/or HHV6 sequences. All biopsies from non-KS tissues (cells) of HIV-positive and HIV-negative individuals were consistently negative for KSHV by PCR. The observation that the same herpes virus-like DNA sequence is present in endemic and sporadic, as well as AIDS-related, Kaposi's sarcoma cases suggests a possible pathogenic association between this putative novel, herpes-like virus and KS. The herpes virus-like DNA sequences described by Y. Chang in 1994 may indeed represent a novel herpes (KSHV), etiopathologically associated with various clinical forms of Kaposi's sarcoma. Its pathogenic importance is indicated by its presence in different KS tissues with various clinical types of KS and its absence from non-KS-involved tissues. Furthermore, the presence of KSHV in KS of children suggests a nonsexual mode of transmission.

Indian state plans compulsory HIV testing, segregation and branding.

PIP: Health officials in the Indian state of Maharashtra have ordered the compulsory testing of all girls 12 years and older who live in designated "destitute homes." The officials also plan to tattoo a symbol on the thighs of all HIV-positive prostitutes. By April 1998, this December 1997 order had resulted in the compulsory testing of women living in 50 boarding houses and the transfer of several found to be HIV-positive to a separate institution 200 miles from the state capital. Nongovernment organizations (NGOs) have mounted a protest over this statute, but state governments in India are free to enact their own health laws. The Maharashtran government is also seeking to legalize prostitution and to force prostitutes to register with a Board that will be able to order compulsory HIV tests and tattooing. Women with HIV who continue to engage in prostitution will be quarantined, and their clients will be jailed. In response, prostitutes in the capital city of Mumbai have threatened to release a list of their client's names to the press. The only recourse available to NGOs who oppose this action is to generate a large enough public outcry to stop it. A Mumbai-based attorney noted that many private companies are also requiring HIV testing and dismissing those who test positive.^ieng

Assessment of sleep after traumatic brain injury (TBI).

BACKGROUND: Individuals who have sustained a TBI often present with complaints of disturbed sleep. Identifying sleep disorders in the TBI population has not been standardized. Much of the confusion may come from the heterogeneity of the research that has been conducted on sleep problems after traumatic brain injury. This review focused attention to current research findings in order to develop an evidenced-based approach to assessment of sleep disturbances within this unique population. OBJECTIVES: To review various methods used in the assessment of disorders of sleep after TBI and offer recommendations for best approaches for clinical assessment of sleep. METHODS: The authors describe various methods such as history, questionnaires, physical examination and objective sleep measurement, their usefulness and limitations based on the available evidence and experience for assessment of sleep in individuals who have sustained a TBI. RESULTS: An evidence-driven method for the assessment of sleep disorders following TBI is discussed. CONCLUSIONS: Through skilled assessment, clinicians can assess sleep following TBI and the most applicable interventions can be chosen with the hopes of reducing additional symptom burden and optimizing functioning.

Office hysteroscopic-guided selective tubal chromopertubation: acceptability, feasibility and diagnostic accuracy of this new diagnostic non-invasive technique in infertile women.

The aim of this study was to evaluate accuracy, tolerability and side effects of office hysteroscopic-guided chromoperturbations in infertile women without anaesthesia. Forty-nine infertile women underwent the procedure to evaluate tubal patency and the uterine cavity. Women with unilateral or bilateral tubal stenosis at hysteroscopy with chromoperturbation, and women with bilateral tubal patency who did not conceive during the period of six months, underwent laparoscopy with chromoperturbation. The results obtained from hysteroscopy and laparoscopy in the assessment of tubal patency were compared. Sensitivity, specificity, accuracy, positive-predictive value and negative-predictive value were used to describe diagnostic performance. Pain and tolerance were assessed during procedure using a visual analogue scale (VAS). Side effects or late complications and pregnancy rate were also recorded three and six months after the procedure. The specificity was 87.8% (95% CI: 73.80-95.90), sensitivity was 85.7% (95% CI 57.20-98.20), positive and negative predictive values were 70.6% (95% CI: 44.00-89) and 94.7% (95% CI: 82.30-99.40), respectively. Pregnancy rate (PR) within six months after performance of hysteroscopy with chromoperturbation was 27%. Office hysteroscopy-guided selective chromoperturbation in infertile patients is a valid technique to evaluate tubal patency and uterine cavity.

Estratégias de ensino do raciocínio clínico nos cursos de Medicina do Brasil - revisão integrativa / Teaching strategies for clinical reasoning in Brazilian medical schools - an integrative review

Resumo: Introdução: O raciocínio clínico é considerado uma das principais habilidades que devem ser desenvolvidas pelos estudantes de Medicina, porque permite a elaboração de hipóteses diagnósticas e orienta estratégias investigativas e diagnósticas de forma racional. Embora os educadores tradicionalmente foquem o ensino no modelo hipotético-dedutivo ou analítico, muitos professores de medicina enfrentam no seu dia a dia o desafio de encontrar novas estratégias para ajudar seus estudantes a desenvolver o raciocínio clínico. Objetivo: Este estudo realizou uma revisão integrativa da literatura para identificar as estratégias utilizadas no processo ensino-aprendizagem do raciocínio clínico, nas escolas médicas brasileiras. Método: A metodologia utilizada consistiu em seis etapas: 1. elaboração da pergunta da pesquisa; 2. definição dos critérios de inclusão e exclusão; 3. elenco das informações a serem extraídas; 4. avaliação dos estudos incluídos; 5. interpretação dos resultados; e 6. apresentação da revisão. Resultado: A maioria dos trabalhos apontam que o ensino do raciocínio clínico é realizado por meio de discussões de casos clínicos, de maneira incidental, em diversas disciplinas ou por meio do uso de metodologias ativas, como PBL, TBL e CBL. Apenas três trabalhos apresentados em congressos demonstraram experiências relacionadas à implantação de uma disciplina curricular obrigatória voltada especificamente ao ensino do raciocínio clínico. O ensino do raciocínio clínico é priorizado no internato em relação às fases clínicas e pré-clínicas. Conclusão: Poucos são os estudos que analisam a maneira como se dá o processo ensino-aprendizagem do raciocínio clínico nas escolas médicas brasileiras. Embora mais estudos sejam necessários, podemos verificar a falta de conhecimento teórico sobre raciocínio clínico como uma das principais causas de dificuldade para o desenvolvimento dessa competência pelos estudantes.

Abstract: Introduction: Clinical reasoning is considered one of the main skills that must be developed by medical students, as it allows the establishment of diagnostic hypotheses and directs investigative and diagnostic strategies using a rational approach. Although educators have traditionally focused the teaching method on the analytical model, many medical professors face the challenge in their daily lives of finding new strategies to help their students develop clinical reasoning. Objective: To carry out an integrative literature review to identify the strategies used in the teaching-learning process of clinical reasoning in Brazilian medical schools. Method: The methodology used consists of six steps: 1. creation of the research question; 2. definition of inclusion and exclusion criteria; 3. list of information to be extracted; 4. evaluation of included studies; 5. interpretation of results and 6. presentation of the review. Results: Most studies indicate that the teaching of clinical reasoning is carried out through discussions of clinical cases, incidentally, in different disciplines or through the use of active methodologies such as PBL, TBL and CBL. Only three studies presented at conferences disclosed experiences related to the implementation of a mandatory curricular discipline specifically aimed at teaching clinical reasoning. The teaching of clinical reasoning is prioritized in internships in relation to the clinical and pre-clinical phases. Final considerations: There are few studies that analyze how clinical reasoning is taught to medical students in Brazilian medical schools. Although more studies are needed, we can observe the lack of theoretical knowledge about clinical reasoning as one of the main causes of the students' difficulty in developing clinical reasoning.

Sperm-related antigens, antibodies, and circulating immune complexes in sera of recently vasectomized men.

Sera from 35 men were collected before and at timed intervals subsequent to vasectomy and examined for the presence of (a) antibody reactive with human spermatozoa, (b) sperm-related antigen, and (c) circulating immune complexes (CIC). Fewer than 10% of the men examined were ever positive for antisperm antibodies. However, sperm-related antigens were elevated in the sera of 18, 18, and 26% of the mean at 2 wk, 2 mo, and 4 mo postvasectomy, respectively. CIC were detected in the sera of some vasectomized men by three different assays. The CIC in patients' sera were precipitated with polyethylene glycol, dissociated, and the individual CIC components identified by an enzyme-linked immunosorbent assay. Most, but not all, of the CIC contained antigen reactive with antisperm immunoglobulin (Ig)G and some also contained complement components C3 and/or Clq. IgA was identified in some of the CIC positive for IgG and sperm antigen and two men had IgM-containing CIC. Analysis of the CIC by sucrose gradient centrifugation revealed them to be heterogeneous in size.

Influence of augmented Hageman factor (Factor XII) titers on the cryoactivation of plasma prorenin in women using oral contraceptive agents.

Prolonged cold storage of plasma may induce the conversion of plasma prorenin (inactive renin) to renin. This phenomenon is exaggerated in oral contraceptive (OC) users; the titer of Hageman factor (HF, Factor XII) in OC users is higher than in nonusers. The present study relates these observations. The increment in plasma renin activity (PRA) during cold storage, as measured by generation of angiotensin I, correlated strongly with the initial plasma titer of HF. Increasing the HF titer of nonusers to that observed in OC users by addition of purified HF increased cold-induced PRA at least twofold, while reducing the plasma HF titer of OC users correspondingly decreased cold-induced PRA. Thus, in OC users, the enhanced conversion of plasma prorenin to renin during cold storage reflects the elevated plasma titer of HF.

PIP: Prolonged cold storage of plasma may induce the conversion of plasma prorenin (inactive renin) to renin. This phenomenon is exaggerated in oral contraceptive (OC) users; the titer of Hageman factor (HF, Factor 12) in OC users is higher than in nonusers. The present study relates these observations. The increment in plasma renin activity (PRA) during cold storage, as measured by generation of angiotensin I, correlated strongly with the initial plasma titer of HF. Increasing the HF titer of nonusers to that observed in OC users by the addition of purified HF increased cold-induced PRA at least 2-fold, while reducing the plasma HF titer of OC users correspondingly decreased cold-induced PRA. Thus, in OC users, the enhanced conversion of plasma prorenin to renin during cold storage reflects the elevated plasma titer of HF.

Long-term vasectomy: effects on the occurrence and extent of atherosclerosis in rhesus monkeys.

We demonstrated previously that atherosclerosis develops more extensively in vasectomized cynomolgus macaques fed an atherogenic diet and speculated that the immunologic response to sperm antigens may have exacerbated the atherosclerosis. We report here that rhesus monkeys vasectomized for 9-14 yr and fed monkey chow (devoid of cholesterol and low in fat) rather than an atherogenic diet also had more extensive and severe atherosclerosis than did control animals of the same age. The extent of atherosclerosis was considered as the percentage of intimal surface with plaques. No control animals were found to have plaques in the thoracic aorta, but 7 of 10 vasectomized monkeys were affected. The plaques in the vasectomized monkeys occupied about 13% of the intimal surface. In 4 of 7 control monkeys and 7 of 10 vasectomized monkeys there were lesions in the abdominal aortas; the lesions were considerably more extensive and severe in the vasectomized animals. Lesions were also more common in iliac arteries of vasectomized animals, and the extent was increased about threefold. Plaques were seen at the carotid bifurcation in all of the animals of both the control and vasectomized groups. The carotid bifurcation plaques of the vasectomized monkeys were larger than those of the control animals on the right but not on the left side. Histologically, the lesions of vasectomized monkeys did not appear to be qualitatively different from those of control animals, even though they were larger and contained more collagen, lipid, and mucopolysaccharides. Grossly, the distribution of the lesions in the vasectomized animals was different from that in the control animals, and that of lesions induced by atherogenic diets, i.e., the lesions were distributed randomly within the artery rather than around bifurcations. More extensive atherosclerosis was noted among vasectomized animals that were found to lack demonstrable circulating free antisperm antibodies. On the basis of the observations made in this study, we suggest that the antisperm antibodies that form after vasectomy may result in circulating immune complexes that exacerbate atherosclerosis.

Mammary tumorigenesis in chemical carcinogen-treated mice. VII. Prolactin and progesterone levels in BALB/c mice.

PIP: Pituitary and serum levels of prolactin (PRL) and serum levels of progesterone (P) were determined by polyacrylamide gel electrophoresis and radioimmunoassays in BALB/c female mice, 15-17 or 44 weeks old, treated with chemical carcinogens. Neither 1.5 mg 3-methylcholanthrene (MCA) nor 1.5-6 mg 7,12-dimethylbenz(a)anthracene (DMBA) markedly altered pituitary or serum levels of PRL in the younger mice, though DMBA increased the total pituitary content of PRL by about 33% in the 44-week-old mice. However, this increase was not correlated with the incidence of mammary tumors in the group or individuals. MCA increased serum P levels by about 22% within 50 days of the last treatment. This increase was attributable to higher serum levels of P during the diestrous and proestrous phases of the cycle. Adrenalectomy reduced serum P levels by about 60%, wheras ovariectomy had no effect. Serum P levels in 44-week-old rats were not affected by DMBA. The results fail to support the notion that MCA and DMBA promote murine mammary tumorigenesis by increasing pituitary and serum prolactin concentrations.^ieng

Her-2/neu and INT2 proto-oncogene amplification in malignant breast tumors in relation to reproductive factors and exposure to exogenous hormones.

In previous studies in southern Sweden, early use of oral contraceptives has been found to be accompanied by an increased risk of developing premenopausal breast cancer, and the tumors developing in these patients have shown a more aggressive behavior. In the present study, amplification of the proto-oncogenes Her-2/neu (also known as ERBB2) and INT2 was studied in primary tumor specimens from 72 premenopausal women and was related to starting age of oral contraceptive use and other reproductive risk factors. Amplification of Her-2/neu was more common among early oral contraceptive users (i.e., those starting at less than or equal to 20 years of age) than among nonusers or late users (odds ratio [OR], 5.3; 95% confidence interval [CI], 1.6-16.7), whereas INT2 amplification did not differ significantly among those groups (OR, 0.9; 95% CI, 0.1-5.0). The likelihood of INT2 amplification was greater among users of progestins and those with a history of abortions before the first full-term pregnancy (OR, 9.0; 95% CI, 1.3-51.7; and OR, 18.6; 95% CI, 2.2-165.8, respectively). No significant relationships were found between proto-oncogene amplification and the variables of parity, age at first full-term pregnancy, or late abortion. The increased ORs persisted after adjustment for age at diagnosis and other risk factors. The findings suggest that the higher rate of Her-2/neu amplification among early oral contraceptive users is an effect of the oral contraceptive use per se rather than of the relative youth of the users. Moreover, the relationship between progestin use and early abortion and amplification of the INT2 gene is biologically plausible.

Determinants of genital human papillomavirus infection in young women.

Carcinoma of the cervix has several well-established epidemiologic risk factors, including multiple sexual partners and early age at first intercourse. Human papillomavirus (HPV) infection appears to have an etiologic role in the development of cervical neoplasia, but evidence linking HPV infection to known risk factors for cervical cancer has been inconsistent. The lack of expected correlations may be due to the inaccuracy of HPV assays previously used. A polymerase chain reaction DNA amplification method for the detection of HPV was used to investigate the determinants of genital HPV infection in a cross-sectional sample of 467 women attending a university health service. In contrast to studies using less accurate detection methods, the risk factors for HPV infection found here were consistent with those for cervical neoplasia. The risk of HPV infection was strongly and independently associated with increasing numbers of sexual partners in a lifetime, use of oral contraceptives, younger age, and black race. Age at first intercourse, smoking, and history of a prior sexually transmitted disease were correlated with, but not independently predictive of, HPV infection. These results demonstrate that the key risk factors for cervical carcinoma are strongly associated with genital HPV infection. This correlation suggests that HPV has an etiologic role in cervical neoplasia and reaffirms the sexual route of HPV transmission.

Potent inhibitory effect of a new antiestrogen (RU 16117) on the growth of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors.

At the daily dose of 24 mug for a period of 4 weeks, RU 16117 (11alpha-methoxyethinyl estradiol), a new antiestrogen, led to 65% reduction of the number of already established dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats. Not only the tumor number but also the tumor size was reduced by RU 16117 in a manner similar to that seen after ovariectomy. The absence of an inhibitory effect of doses of 0.1 to 12.5 mug 17beta-estradiol (E2) per day, a dose-range which covers the low estrogenic activity of the RU 16117 doses used, suggested that the inhibitory effect of RU 16117 was not due to its estrogenic activity. Decreased levels of receptors for E2, progesterone, and prolactin were found in the tumors remaining after ovariectomy; treatment with the dose of RU 16117 sufficient to inhibit tumor growth (24 mug) had a similar inhibitory effect on the levels of E2 and prolactin receptors. These data suggested that a reduction of hormone receptor levels in the tumor tissue could be a mechanism by which RU 16117 acts as a potent inhibitor of the growth of DMBA-induced mammary carcinoma.

PIP: The new antiestrogen RU 16117, at doses of 8 or 24 mcg daily, had been shown to completely prevent the development of rat mammary cancer when given from the day after 7,12-dimethylbenz(a)anthracene (DMBA) administration. This study was undertaken to investigate the effect of this compound on the growth of DMBA-induced tumors which had already developed in Sprague-Dawley rats. The effect was compared with that of castration. Levels of receptors for 17beta-estradiol (E2), progesterone, and prolactin (PRL) were correlated with the response. At about 3 months after DMBA administration animals with palpable tumors were selected. The rats were then treated daily for 4 weeks with .1, .5, 2.5, or 12.5 mcg E2 or with 2, 8, or 24 mcg RU 16117 injected in .1 ml of 1% gelatin in .9% NaCl. Controls were injected with the vehicle alone. For comparison, a group of rats were ovariectomized. After 4 weeks' treatment rats were killed, blood collected, and a cytosol was prepared from tumor tissues. Binding assays and radioimmunoassays were done. 8 and 24 mcg doses of RU 16117 led to 45 and 65% inhibition of tumor number, respectively, and tumor size was markedly reduced. Lower doses had less effect. Ovariectomy had an effect similar to that of 24 mcg RU 16117. E2 doses did not change the number or size of tumors. Decreased levels of receptors for E2, progesterone, and PRL were found in the tumors remaining after ovariectomy. The 24 mcg dose of RU 16117 had a similar effect on levels of E2 and PRL receptors. It was considered likely that RU 16117 exerts its inhibitory activity at both the hypothalamic-pituitary and tumor levels.

Invasive cervical cancer and smoking in Latin America.

A case-control study of 667 patients with invasive squamous cell carcinoma of the cervix and 1,430 controls from four Latin American countries showed an age-adjusted relative risk (RR) of 1.2 [95% confidence interval (CI) = 1.0-1.4] for women who had ever smoked, with risk rising to 1.7 (95% CI, 0.8-3.6) for women who smoked greater than or equal to 30 cigarettes per day. The associations were practically eliminated after adjustment for the number of sexual partners and alcohol consumption, probably a surrogate for an unidentified life-style risk factor. Some excess risk persisted among women who smoked for extended periods (RR = 1.5 for greater than or equal to 40 yr), as well as those who began smoking at older ages (RR = 1.7 for greater than 30 yr), which suggests a late-stage effect. In addition, among women who tested positive for human papillomavirus (HPV) type 16 or 18 by filter in situ hybridization, there was an increased risk for women who had ever smoked and a dose-response relationship with the number of cigarettes smoked (adjusted RRs compared with HPV-negative nonsmokers = 5.0 for HPV-positive nonsmokers, 5.5 for less than 10 cigarettes/day, and 8.4 for greater than or equal to 10 cigarettes/day). In contrast, HPV-negative women had no increased risk associated with smoking. These results, from a high-incidence area where intensive smoking among women is still relatively rare, suggest that smoking has a limited effect on cervical cancer risk, possibly only among women with specific types of HPV.

Role of prolactin in rat mammary carcinogenesis: detection of carcinogenicity of low-dose carcinogens and of persisting dormant cancer cells.

PIP: Rats used were W/Fu strain with a reported incidence of spontaneous mammary tumors (MTs) of 17%. Most of these have been benign fibroadenomas in older females. X-ray or fast neutron irradiations were given in subthreshold doses, some as low as 10 rads. Also, low doses (150 mg) of a chemical carcinogen (N-nitroso-N-butylurea; NBU) prolactin (MtH). The prolactin was provided by grafting a syngeneic mammatropic pituitary tumor (MtT.W95 or MtT.W98). Tumors developing at the implantation site were chormophobe adenomas. The latent period of tumor induction decreased after the 4th generation of animal passage of the tumors. In some rats, ovariectomy was done 1 week before X-irradiation. No MT was found in 18 untreated controls during 1 year of observation. No MT developed in 32 rats having only the grafts for 9-12 months. Total-body-X-irradiation with 25 or 50 rads alone elicited no MT for 1 year. Among 27 rats exposed to 200 rads of X-rays 2 developed MT fibroadenomas after 5 and 7 months. The supplemental administration of prolactin greatly increased and accelerated the occurrence of MTs in irradiated rats. Most of these were adenocarcinomas. Ovariectomized rats had fewer MTs than intact females. A correlation was found between dose and MT incidence. The persistence of chemically transformed MT cells was shown by the addition of prolactin several months after NBU therapy. MTs developed in 8 of 10 rats within 3 months after the MTT graft became palpable. All but 1 of these were adenocarcinomas. Apparently there had been no repair or elimination of damaged cells in the dormant state. It is suggested that progressive growth of MTs may depend on the hormonal milieu of the host.^ieng

Experts confer on vasectomy and prostate cancer risk.

PIP: In March 1993, physicians attended a US National Institutes of Health (NIH) conference on a possible association between vasectomy and prostate cancer. Participants learned that some studies have found an association while others have not. The strongest evidence of an association is a small association. The inconsistency of the results of various studies and the lack of a convincing biological mechanism satisfied participants that no need exists to recommend changes in clinical and public health practice. 2 recent, well-controlled studies, conducted by researchers at Brigham and Women's Hospital in Boston, Massachusetts, published in the Journal of the American Medical Association found around a 60% increase in risk of developing prostate cancer in men with vasectomies. It found a decreased risk for overall mortality among vasectomized men, however. These studies prompted a call for this NIH conference. Studies prior to these Boston studies had methodological flaws, especially detection bias. Specifically, urologists are more likely to examine men with vasectomies and, therefore, diagnose prostate cancer. A well-controlled, large-scale, case control study in California published in 1991 and its follow-up study did not find an increased risk of prostate cancer in vasectomized men. The follow-up study found a decreased risk for overall mortality among men with vasectomies. The lack of knowledge about the etiology of prostate cancer is the biggest roadblock to understanding the link between vasectomy and prostate cancer. Suggested mechanisms explaining vasectomy's ability to increase prostate cancer risk include changes in hormone levels, immunologic responses, and changes in levels of cancer-promoting growth factors or inhibitors of these factors.^ieng