Diagnostic significance of 'benign pairs' and signet ring cells in fine needle aspirates (FNAs) of the breast

Most breast mass lesions are readily characterized by FNA with cytodiagnosis. Occasionally, benign but markedly proliferative lesions are diagnostically difficult to separate from well differentiated malignancies. We present information pertaining to the diagnostic significance of two cytologic findings observed in breast aspiration specimens, namely pairs of stripped bipolar nuclei and signet ring cells (SRC). We have evaluated aspirate smears from 219 cases of histologically proven benign (n = 114) and malignant (n = 105) breast lesions. Both singlets and pairs of bipolar nuclei and SRC were enumerated, and their numbers were correlated to histological diagnosis. Closely associated pairs of stripped bipolar nuclei were found in 68% of benign lesions compared with only 3.8% of carcinomas, establishing their presence as a highly specific indicator of a benign process. Large numbers of such 'benign pairs' also favoured the diagnosis of fibroadenoma. SRC were identified in 66% of histologically proven carcinomas (67% of ductal and 70% of lobular). SRC were also present in 10% of histologically benign cases. In the malignant cases, SRC were most frequently noted in a single cell distribution or within small, loosely cohesive tissue fragments. In the benign instances, SRC were most commonly noted within large fragments, and many of these cells were proved by immunohistochemical reactions to be vacuolated myoepithelial cells. We conclude that the presence of bipolar nuclei in closely associated pairs suggests benignity and aids in the subclassification of benign breast masses. In addition, the presence of SRC does not aid in the classification of tumour subtype (ductal vs lobular), and the occurrence of such cells in the proper context should prompt surgical biopsy.     

Prevalence and connotative meaning of cigarette smoking among Thai adolescents and young adults

Prevalence and evaluative opinions about smoking among 527 adolescents and young adults were quantified in order to assess the efficacy of Thailand's mass media antismoking campaign. The reactions of subjects to the smoking of (a) father, (b) mother, (c) boys, (d) girls, and (e) myself were obtained using a semantic differential measure. Virtually all subjects had seen antismoking adds on television and the overall perception of smoking was highly disapproving with significant gender and age differences being present. Older males were more likely to smoke and had less critical attitudes about this harmful behavior than their younger peers and female participants. Reactions to female smoking (mother and girls) were more derogatory than to the same behavior among males (father and boys). Results suggest that smoking will continue as a serious problem among Thai males and demonstrate the addictive nature of cigarette smoking which persists in spite of the increasingly negative evaluative attitudes of users.     

Role of leukotrienes revealed by targeted disruption of the 5-lipoxygenase gene

Leukotrienes constitute a class of potent biological mediators of inflammation and anaphylaxis (for reviews see refs 1 and 2). Their biosynthesis derives from 5-lipoxygenase-catalysed oxygenation of arachidonic acid in granulocytes, macrophages and mast cells. To examine the physiological importance of leukotrienes, we have disrupted the 5-lipoxygenase gene by homologous recombination in embryonic stem cells. 5-Lipoxygenase-deficient (5LX-/-) mice develop normally and are healthy. They show a selective opposition to certain inflammatory insults. Although there is no difference in their reaction to endotoxin shock, the 5LX-/- animals resist the lethal effects of shock induced by platelet-activating factor. Reaction to ear inflammation induced by phorbol ester is normal, whereas inflammation induced by arachidonic acid is markedly reduced. Contrasts were also found in two models of leukocyte chemotaxis in vivo. The phenotype of 5LX-/- mice under injurious insult identifies the role for leukotrienes in the pathophysiology of select inflammatory states.     

Maintenance of remission of ulcerative colitis: a comparison between balsalazide 3 g daily and mesalazine 1.2 g daily over 12 months. ABACUS Investigator group

BACKGROUND: Despite widespread use of aminosalicylates as maintenance treatment for ulcerative colitis (UC), patients still report troublesome symptoms, often nocturnally. AIM: To compare the efficacy and safety of balsalazide (Colazide) with mesalazine (Asacol) in maintaining UC remission. METHODS: A randomized, double-blind comparison of balsalazide 3 g daily (1.04 g 5-ASA) and mesalazine 1.2 g daily for 12 months, in 99 (95 evaluable) patients in UC remission. RESULTS: Balsalazide patients experienced more asymptomatic nights (90% vs. 77%, P=0.0011) and days (58% vs. 50%, N.S.) during the first 3 months. Balsalazide patients experienced more symptom-free nights per week (6.4+/-1.7 vs. 4.7+/-2.8; P=0.0006) and fewer nights per week with blood on their stools or on the toilet paper, mucus with their stools or with sleep disturbance resulting from symptoms or lavatory visits (each P < 0.05). Fewer balsalazide patients relapsed within 3 months (10% vs. 28%; P=0.0354). Remission at 12 months was 58%, in both groups. Similar proportions of patients reported adverse events (61% balsalazide vs. 65% mesalazine). There were five serious adverse events (two balsalazide, three mesalazine) and four withdrawals due to unacceptable adverse events (three balsalazide, one mesalazine), of which one in each group was also a serious adverse event. CONCLUSIONS: Balsalazide 3 g/day and mesalazine 1.2 g/ day effectively maintain UC remission and are equally well tolerated over 12 months. At this dose balsalazide prevents more relapses during the first 3 months of treatment and controls nocturnal symptoms more effectively.     

Discontinuation of treatment with IFN-beta leads to exacerbation of experimental autoimmune encephalomyelitis in Lewis rats. Rapid reversal of the antiproliferative activity of IFN-beta and excessive expansion of autoreactive T cells as disease promoting mechanisms

BACKGROUND: It is important for HIV/AIDS control programmes to determine population knowledge on AIDS in order to develop appropriate Information, Education and Communication (IEC) messages. The objectives of our study were to determine the seroprevalence of HIV and syphilis among pregnant women, female prostitutes and long-distance truck drivers and to evaluate knowledge, attitudes, beliefs, and practice (KABP) with respect to the HIV/AIDS epidemic in these three groups in Burkina Faso. METHODS: We performed three cross-sectional serosurveys including face-to-face interviews on KABP between October 1994 and February 1995 in three population groups. RESULTS: Overall, 1,294 pregnant women, 236 long-distance truck drivers and 426 female prostitutes were recruited. HIV seroprevalence was 8% (95% Confidence Interval (CI): 6.6-9.6) among pregnant women, 18.6% (95% CI: 13.9-24.2) among long-distance truck drivers and 58.2% (95% CI: 53.4-62.9) in female prostitutes. The prevalence of syphilis was 2.5%, 9.3% and 15%, respectively. Most pregnant women (98%), long-distance truck drivers (96%) and female prostitutes (98%) had already heard of AIDS. However, the level of knowledge of HIV transmission routes, of risk factors for HIV transmission and of available preventive measures was very low. Consequently, 41% of pregnant women, 40% of long-distance truck drivers and an alarming 61% of female prostitutes reported that they did not feel themselves at risk for HIV. In each group, high levels of knowledge on AIDS were associated with increased awareness of AIDS risk and the adoption of preventive behaviours. Level of education was associated with knowledge of AIDS and condom use. However, in the 12 months preceding the surveys, condom use was very low among pregnant women (0.1%), long-distance truck drivers (18%) and among female prostitutes (42%). CONCLUSIONS: These results indicate that HIV is widespread in Burkina Faso and that there is an urgent need to develop and evaluate HIV prevention strategies in the general population and among core groups such as female prostitutes and long-distance truck drivers. Interventions must include information campaigns, condom promotion and distribution, and sexually transmitted diseases control.     

Cloning and characterization of the NAD-linked glycerol-3-phosphate dehydrogenases of Trypanosoma brucei brucei and Leishmania mexicana mexicana and expression of the trypanosome enzyme in Escherichia coli

A polyclonal antiserum raised against the purified glycosomal glycerol-3-phosphate dehydrogenase of Trypanosoma brucei brucei has been used to identify the corresponding cDNA clone in a T.b. brucei expression library. This cDNA was subsequently used to obtain genomic clones containing glycerol-3-phosphate dehydrogenase genes. Two tandemly arranged genes were detected in these clones. Characterization of one of the genes showed that it codes for a polypeptide of 353 amino acids, with a molecular mass of 37,651 Da and a calculated net charge of +8. Using the T.b. brucei gene as a probe, a corresponding glycerol-3-phosphate dehydrogenase gene was also identified in a genomic library of Leishmania mexicana mexicana. The L.m. mexicana gene codes for a polypeptide of 365 amino acids, with a molecular mass of 39,140 Da and a calculated net charge of +8. The amino-acid sequences of both polypeptides are 63% identical and carry a type-1 peroxisomal targeting signal (PTS1) SKM and -SKL at their respective C-termini. Moreover, the L.m. mexicana polypeptide also carries a short N-terminal extension reminiscent of a mitochondrial transit sequence. Subcellular localisation analysis showed that in L.m. mexicana the glycerol-3-phosphate dehydrogenase activity co-fractionated both with mitochondria and with glycosomes. This is not the case in T. brucei, where the enzyme is predominantly glycosomal. The two trypanosomatid sequences resemble their prokaryotic homologues (32-36%) more than their eukaryotic counterparts (25-31%) and carry typical prokaryotic signatures. The possible reason for this prokaryotic nature of a trypanosomatid glycerol-3-phosphate dehydrogenase is discussed.     

Conditions for the induction of long-term potentiation in layer II/III horizontal connections of the rat motor cortex

1. The present studies investigated conditions for the induction of long-term potentiation (LTP) in the local horizontal pathways of layers II/III in the primary motor cortex (MI) of the adult rat. Field potential and intracellular recordings demonstrated synaptic interactions across the superficial layers within MI that could be enhanced transiently by focal application of the gamma-aminobuturic acid-A receptor antagonist bicuculline methiodide (Bic) at the recording site. 2. Field potentials evoked in the superficial MI horizontal pathways increased in amplitude after tetanizing, theta burst stimulation (TBS), but only when Bic was applied transiently at the recording site immediately before TBS. In the absence of Bic, TBS failed to produce long-lasting increases in horizontally evoked field responses. By contrast, TBS delivery during focal Bic application increased field potential amplitudes by 25-35% when measured 25-30 min after stimulation. The amount of potentiation was greater when two converging horizontal inputs were stimulated together but was not increased with higher intensity stimulation. Persistent effects of Bic application alone were evident. However, these effects were small unless Bic application continued until evoked field potential amplitude increase exceeded 200% of baseline. 3. The synaptic nature of field potential increases were confirmed using intracellular recordings of layer II/III neurons located near field potential electrodes. 4. LTP also could be induced without Bic application by cotetanization of vertical pathways simultaneously with horizontal activation. Vertical conditioning alone at 2 Hz, which affects inhibitory efficacy, was shown to transiently relieve depression of successive responses that ordinarily occurs during a burst of three horizontal stimuli. These results suggest that LTP of horizontal pathways may be regulated by spatiotemporal interactions between horizontal and vertical pathways. 5. Horizontal LTP was blocked reversibly by bath application of the N-methyl-D-aspartate (NMDA) antagonist 2-amino-5-phosphonovaleric acid, thereby implicating NMDA-receptor activation in LTP induction for these pathways. 6. The results confirm and extend our previous finding that the potential for activity-dependent modification of synaptic connections exists within the intrinsic horizontal connections of the superficial cortical layers. Synaptic modification across horizontally connected neurons appears to be regulated both by the arrangement of intrinsic circuitry and by the availability of mechanisms for modification at individual synapses. The properties of horizontal connections indicate that they form a spatial substrate and provide an activity-dependent mechanism for plasticity of adult cortical representations.     

Immunization status and sociodemographic characteristics: the mediating role of beliefs, attitudes, and perceived control

OBJECTIVES: This study examined how immunization-related beliefs, attitudes, and perceived control mediate up-to-date immunization among various sociodemographic groups. METHODS: Statewide estimates of immunization rates among children up to the age of 2 years were obtained via a multistage cluster sample. In-person interviews were conducted with 4832 parents. Information about immunization was obtained from official records or from health care providers. RESULTS: Differences in immunization among sociodemographic groups were mediated by beliefs about objective barriers to immunization, protection, medical contraindication, safety concerns, distrust, and natural immunity. Protection beliefs contributed to positive attitudes toward immunization; beliefs in natural immunity and safety concerns contributed to negative attitudes. Beliefs about objective barriers, distrust, safety concerns, and medical contraindications influenced perceived control over immunization. Positive attitudes and a strong sense of control contributed to higher immunization rates. CONCLUSION: These findings provide a basis for efficient educational campaigns by specifying which beliefs should be bolstered (because they facilitate proper immunization) and which should be targeted for change (because they hinder proper immunization) in various sociodemographic groups.     

Toxoplasma gondii recombinant antigens H4 and H11: use in ELISAs for detection of toxoplasmosis in swine

The prevalence of elevated blood lead (PbB) levels in rural and semi-urban areas of Kwazulu/Natal (KZN) as well as the risk factors for elevation of PbB among children in informal settlements are examined. The study involved over 1200 children in two age groups: 3-5 and 8-10 years old. Average PbB level in Besters, an informal settlement in the Durban metropolitan region, was 10 micrograms/dl with 5% of the children showing PbB level of greater than 25 micrograms/dl. By comparison, average PbB value in Vulamehlo, a rural area located 90-120 km from Durban, was 3.8 micrograms/dl and 2% of the PbB was greater than 10 micrograms/dl. The results show that many children in KZN are at risk of being lead poisoned. Household factors that were significantly associated with PbB levels in children included distance from tarred roads, overcrowding, hygienic habits in the household and the burning of solid wastes for heating or cooking. Lack of significant association with child risk behaviors is attributed to the over-riding influence of high levels of contaminated dusts both indoor and outdoor. With recent introduction of unleaded gasoline in South Africa, a number of unique socio-ecological factors are expected to slow the change in PbB levels of children in some townships.