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.

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.

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

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.

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.

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.

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.

Effects of progesterone on the response to epidermal growth factor and other growth factors in cultured human meningioma cells.

The presence of receptors for progesterone in a large proportion of human meningioma tissues is well established. The occurrence of increased rates of growth of meningiomas in situ during pregnancy suggests the existence of a relationship between high progesterone levels and the growth of meningiomas. However, experiments with cultured meningioma tissue (cells or explants) have shown only minimal effects of progesterone. It has been shown recently that many meningiomas have receptors for epidermal growth factor. In this paper we have investigated the response of cultured human meningioma cells to epidermal growth factor and other growth factors and the modulation of this response by progesterone and the progesterone-receptor blocking agent mifepristone (RU 38486). The results suggest that the presence of progesterone in the culture medium increases the sensitivity of meningioma cells to mitogenic stimuli, whereas mifepristone can counteract the stimulating effects of progesterone.

Radioimmunoassay of rat 1 -fetoprotein.

PIP: A competitive binding radioimmunoassay for rat alpha 1 fetoprotein (AFP) was developed, using Sprague-Dawley rat amniotic fluid. The assay was approximately 20,000 times more sensitive than double-diffusion in agar for AFP detection; the assay threshold was 5 ng. Further purification of apparently pure (by immunodiffusion and immunization) radiolabeled AFP was required for the specific assay. An assay for a previously undetected contaminant(s) was used to check the purity of rat AFP isolated by isoelectric focusing to obtain the purified unlabeled AFP needed to establish the standard inhibition curve. All procedures are outlined.^ieng

Radioimmunoassay for 1 -fetoprotein in the serum of rats.

PIP: A radioimmunoassay (RIA) method for alpha 1-fetoprotein (AFP) in the serum of rats is reported. The method is based on the preparation of purified and radiolabeled AFP, monospecific anti-AFP antiserum, and a modification of the coprecipitation-inhibition technique in 50% saturated ammonium sulfate. A combination of immunochemical and physiocochemical methods are used in the purification of the AFP. The purified AFP is virtually identical to the native, circulating AFP by immunological criteria and contains, at most, trace contamination with other materials. The RIA has a sensitivity that allows 25 ng AFP/ml of serum to be detected with reproducibility. This assay requires 20 mcl of serum and can be completed within a few hours. It is concluded that this RIA, dependent upon the preparation of monospecific anti-AFP, radioiodination of highly purified rat AFP and a modified Farr procedure, is a sensitive and reproducible RIA.^ieng

Regional distribution of human papillomavirus DNA and other risk factors for invasive cervical cancer in Panama.

A population-based national cancer registry has documented strikingly different regional incidence rates of cervical cancer in the Republic of Panama. Such regional differences in disease rates could represent regional differences in the occurrence of risk factors, in particular, human genital papillomaviruses (HPV). This study enrolled newly diagnosed invasive cancer patients in the Republic of Panama over an 18-mo period. Behavioral risk factors were measured by interviewing cases and matched controls. In addition, DNA extracted from biopsies of the cancers was tested for HPV sequences. Early age at first coitus, multiple pregnancies, and nonparticipation in Pap smear screening programs were significant risk factors for cervical cancer in this population. These factors and low levels of education occurred more frequently among women residing in regions with higher cancer rates than women residing in the region with lower cancer rates. HPV DNA was detected most frequently (70%) among cases from the region with the lowest cancer rate (30 of 100,000) and least frequent (54%) among cases where the cancer rate was the highest (51 of 100,000). The observations suggest that risk factors other than HPV contribute to the differences in cervical cancer rates among women residing in various regions of Panama.

Oral contraceptive use, human papillomavirus infection, and risk of early cytological abnormalities of the cervix.

Oral contraceptive (OC) use was examined as a risk factor for cytological abnormalities of the cervix among 1964 women receiving Papanicolaou smears at three hospitals in the Washington, D.C., area. A single pathologist classified cytological results from all women as normal (n = 1423), atypia (n = 314), low grade squamous intraepithelial lesion (SIL; n = 208), or high grade SIL (n = 19). Women in each of the three abnormal groups were compared to women with normal cytological diagnoses. A subset of 579 patients, including most of the women with low or high grade SIL and a matched group of controls, was tested for human papillomavirus (HPV) by type-specific Southern blot hybridization to examine the effects of OC use while taking into account the effects of HPV infection. OC use was found to be unrelated to risk of atypia or low grade SIL but was associated with an elevated risk of high grade SIL that increased with longer duration of use (relative risk = 4.6, 95% confidence interval = 1.1-18.1 for greater than or equal to 5 years of use). HPV infection was associated, as expected, with risk of low and high grade SIL but not with atypia. Taking the HPV results into consideration did not alter the OC findings. There was no evidence that OC use synergistically increased the risk of cervical neoplasia among HPV-infected women, although small numbers prevented a reliable evaluation for high grade SIL. OC use did appear to increase the detection of HPV types 16/18, but the etiological importance of this finding is unclear.

Ultrastructural and morphometric study of diethylstilbestrol-associated lesions diagnosed as cervical intraepithelial neoplasia III.

Investigations were carried out to characterize diethylstilbestrol (DES)-associated squamous lesions and to assess their biological significance. Five DES-associated cervical lesions displayed architectural features which were diagnosed as cervical intraepithelial neoplasia (CIN) III, such as full-thickness replacement by atypical squamous cells with vertical orientation and absence of normal polarity. Electron microscopic examination revealed only one of the five to be consistent with the generally recognized ultrastructural picture of non-DES CIN III. In the remaining four lesions, the moderate-to-large numbers of tonofibrils and well-developed desmosomes distinguished them from the true CIN III lesions. Morphometric studies indicate the five DES-associated lesions in this study as a group to be significantly different from normal squamous epithelium, from maturing metaplasia, and from non-DES-related CIN III in the parameters of differentiation studied. Their intermediary position between maturing metaplasia and non-DES CIN III suggests that they are more differentiated than CIN III and less differentiated than maturing metaplasia. Nuclear area measurements indicate the increased nuclear-cytoplasmic ratio observed in the DES-associated CIN III lesions of this study is due to a decrease in cytoplasmic volume, as opposed to an increased nuclear size.

PIP: 5 diethylstilbestrol (DES)-associated squamous lesions, all of which had been diagnosed as cervical intraepithelial neoplasia 3 (CIN 3), were investigate to assess the biological significance of these lesions among women exposed in utero to DES. The diagnoses were based on characteristics such as full-thickness replacement by atypical squamous cells with vertical orientation and absence of normal polarity. However, by electron microscopic techniqeus it was found that only 1 of the 5 lesions was consistent with the generally recognized ultrastructural look of non-DES-associated CIN 3. The remaining 4 leasions had in architecture moderate-to-large numbers of tonofibrils and well-developed desmosomes which distinguished these lesions from true CIN 3 lesions. A morphometric study indicated that the 5 DES-associated lesions studied here are significantly different from normal squamous epithelium, from maturing metaplasia, and from non-DES-related CIN 3, suggesting that they are more differentiated than CIN 3 and less differentiated than maturing metaplasia. When nuclear areas were measured in these lesions, increased nuclear-cytoplasmic ratio was observed in the DES-associated CIN 3 lesions, caused by decreased cytoplasmic volume rather than increased nuclear size.

AIDS in Haitian-Americans: a reassessment.

PIP: The occurrence of acquired immunodeficiency syndrome (AIDS) in Haitians and Haitian-Americans has remained an enigmatic aspect of the AIDS mystery. Although Haitians are currently classified as a high risk group, this designation has been disputed. The incidence of AIDS in recent Haitian immigrants to the US has been estimated at 84/100,000, which is lower than the 200-240/100,000 figure put forward for other risk groups. To better understand the spread of AIDS within the Haitian population, a serologic study of human T-lymphotropic virus type III (HTLV-III) seropostivity was performed on 88 healthy Haitians and 21 Haitians with AIDS in New York City. 95.2% of Haitian AIDS patients compared with only 1.1% of controls had a positive ELISA for HTLV-III infection. The low rate of seropositivity in health Haitians contrasts sharply with the prevalence of seropositivity noted in other high risk groups. For example, HTLV-III antibodies have been detected in 53% of healthy New York homosexuals and over 60% of drug users in New York and New Jersey. A likely explanation is that only a small segment of Haitian-Americans are really at risk of HTLV-III infection, and that this risk is conferred not by practices widespread in the Haitian community but by homosexuality, drug abuse, blood transfusions, or other as yet unidentified modes of transmission. Support for this thesis is provided by data from Haiti, where AIDS cases have been associated with bisexuality, an extremely high prevalence of veneral diseases, and contact with prostitutes. It is concluded that the designation of the entire Haitian community as a high risk group for AIDS may be inappropriate.^ieng

Unique pattern of HTLV-III (AIDS-related) antigen recognition by sera from African children in Uganda (1972).

Of 75 sera collected in the West Nile district of Uganda over a 1-year period between 1972 and 1973, 50 (66%) had antibody reactivity to human T-cell lymphotropic virus subgroup III (HTLV-III) at low titer levels. Sera were initially screened by HTLV-III enzyme linked immunosorbent assay and sera with values less than normal mean + 2 SD were removed from testing. The remaining sera were tested for positivity by an amplified Western blotting procedure which incorporated a three-layer immunoperoxidase procedure. Immunoglobulin reactive with HTLV-III Mr 24,000, 41,000, and 76,000 proteins were present in nearly all positive sera. The antibody status of this group was unlike any normal or acquired immunodeficiency syndrome-risk group previously tested. The high prevalence and relatively low titers suggest the detection as early as 1972 of a relative or predecessor of HTLV-III or of HTLV-III itself but existing in a population acclimated to its presence. It further suggests a likely African origin of HTLV-III.

PIP: Sera from 75 children from an isolated subsistence farming region of the Ugandan Nile valley in 1972-1973 showed a unique pattern of antibody titer to HTLV-III: a high prevalence but low titer for a limited number of viral proteins. The sera were originally collected at random as controls for a study of Burkitt's lymphoma. Mean age was 6.4 years. Sera were tested quantitatively by ELISA and 50 of 55 positives were confirmed by Western blot. The most prominent bands had molecular weights of 76,000, 41,000 and 24,000, coinciding with HTLV-III antigens previously described. The geometric mean titer was 295 with a range of 100-1000. The results suggest high prevalence of a closely related virus in this population.

Early appearance of serum -fetoprotein during hepatocarcinogenesis as a function of age of rats and extent of treatment with 3'-methyl-4-dimethylaminoazobenzene.

PIP: The early appearance of serum alpha-fetoprotein (AFP) during hepatocarcinogenesis as a function of age of rats and extent of treatment with 3'-methyl-4-dimethylaminoazobenzene is reported. Administration of .06% of the benzene hepatocarcinogen in the diet of 6- to 12-week-old male rats led to the prompt appearance of AFP in the serum within 3-4 weeks. Discontinuation of treatment at Week 5 dropped the AFP in serum to undetectable levels within 2 weeks, and it remained negative over a 30-week period when, at autopsy, no liver cancer was found. Administration of azo dye to 6-week-old rats for 10 weeks also decreased AFP in serum to undetectable levels over the next 2 weeks, except in 2 of 45 rats who developed large hepatomas early and remained positive. In the remainder, AFP reappeared beginning at Week 15, and liver cancer was present at Week 20 except for 13 rats that remained negative, although 7 had hepatoma. The age of the rats played no marked role in the precocious appearance of AFP. The presence of AFP in each group was related to the histological picture of the liver at the time of autopsy. There was no detectable AFP in untreated control rats, nor was there any in rats fed .05% of the hepatotoxic but not carcinogenic alpha-naphthylisothiocyanate which led to extensive jaundice and bile duct proliferation.^ieng