Benzo[a]pyrene at an environmentally relevant dose is slowly absorbed by, and extensively metabolized in, tracheal epithelium

While tobacco smoke has been conclusively identified as a lung carcinogen, there is much debate over which smoke constituent(s) are primarily responsible for its carcinogenicity. Previous studies in our laboratory suggested that highly lipophilic carcinogens are slowly absorbed in the thicker epithelium of the conducting airways, potentially allowing for substantial local metabolism. The bioactivation of polycyclic aromatic hydrocarbons in airway epithelium may, hence, be important in tobacco smoke-induced carcinogenesis. In the present study, the hypothesis of slow absorption and substantial local metabolic activation of highly lipophilic carcinogen in airway epithelium was tested in dogs. A single dose of tritiated benzo[a]pyrene (BaP) dissolved in a saline/phospholipid suspension was instilled in the trachea, just anterior to the carina. At intervals of a few minutes up to 30 min over a 3-h period, blood samples were drawn from the azygous vein, which drains the area around the point of instillation, and from the systemic circulation. Tissue samples were taken at the end of the experiment. The concentration of BaP with depth into the tracheal mucosa was determined with autoradiography. BaP was slowly absorbed into the trachea with a half-time of approximately 73 min, which is consistent with diffusion-limited passage through the epithelium and lead to local doses in the tracheal epithelium that were more than a 1000-fold those of other tissues. The long retention of BaP in the epithelium provided the local metabolizing enzymes with high substrate levels over a long period, resulting in extensive metabolism. At 3 h after the exposure, 23% of the BaP-equivalent activity remained in the tracheal mucosa. Of this fraction, 13% was parent compound, 28% was organic extractable, 31% was water-soluble, and 28-7% of the instilled dose was bound to tracheal tissues. These results explain the tendency of highly lipophilic carcinogens, such as BaP, to induce tumors at the site of entry and, furthermore, indicate that the highly lipophilic components of tobacco smoke and polluted air may be the most important contributors to lung tumors of the conducting airways.      

Need for follow up in coeliac disease

The use of follow up studies was evaluated in 128 patients with coeliac disease during their first visit to a department for adults. The original diagnosis had been made in childhood in all patients. Fifty eight (45%) of the subjects were following a gluten free diet, 23 (18%) were following a gluten free diet but with occasional gluten consumption, and 47 (37%) had adopted an unrestricted, gluten containing diet for a mean of 11.2 years. There was no correlation in individual subjects between the presence of symptoms, biochemical and immunological abnormalities, severity of histological findings, and the amount of dietary gluten, despite the greater frequency of symptoms in the group following an unrestricted diet than in the other two groups. Short stature and epilepsy with cerebral calcifications only occurred in patients following an unrestricted diet. As only diagnosis based on two or three biopsy samples and regular follow up correlated positively with dietary compliance, it is suggested that a histologically confirmed diagnosis of coeliac disease and regular lifelong follow up are essential in the management of these patients.     

Elderly Patients with Suppressed Serum TSH but Normal Free Thyroid Hormone Levels Usually Have Mild Thyroid Overactivity and are at Increased Risk of Developing Overt Hyperthyroidism

The clinical and biochemical characteristics of 15 elderly patientswith low levels of thyrotrophin (TSH) (<0.1 mU/L) but normalfree tri-iodothyronine, (T3) and free thyroxine (T4) (groupS) were compared with 10 euthyroid subjects (group E) and 10hyperthyroid patients (group T). Free T3 and free T4 were significantlyhigher (p<0.05) in group S(6.3±0.5 and 18.6±1.0pmol/l, respectively) than in group E(4.6±0.3, 12.6+0.6).In common with elderly hyperthyroid patients (group T)patientsin group S had few signs or symptoms of thyrotoxocosis, butthe Wayne score (clinical index of hyperthyroidism) was higherin group S than in euthyroid subjects (p<0.05). Thyroid microsomal,thyrogolobulin or thyrotrophin receptor antibodies were commonin group T (n=9)but not in groups S(n=2) or E(n=1). This suggestsa low prevalence of Graves' disease in group S compared to groupT. Combined thyrotrophin releasing hormone (TRH; 200 µgi.v.) and gonadotrophin releasing hormone GnRH; 100 µgi.v.) tests were performed; no cases of low TSH due to hypopituitarismwere identified in group S. During a mean of 7.9 (4–12)months of observation TSH reverted to the normal range (>0.2mU/L)in 7 of 15 patients in group S; thyroid hormone concentrationsrose above the normal range in four, however, only two patientsrequired treatment for hyperthyroidism. It is unlikely thatthe suppressed TSH of patients in group S was due to mild thyroidhormone excess; although this is often a transitory phenomenon,these patients are at increased risk of developing overt hyperthyroidism.     

Applications of ultrasound in dentistry

An ultrasonic descaler working at kHz frequencies is used in dentistry to remove attached deposits from the teeth. Such devices offer many advantages over conventional hand instruments by reducing both the work and time involved in the clinical descaling process. Although it is a recognised clinical instrument, there has been little attempt to standardise its acoustic power output. A parameter which may characterise adequately the acoustic emission from these instruments is the displacement amplitude of the probe tip. Modification of the ultrasonic descaler generator has led to the further use of the instrument in other dental areas. Diagnostic applications of MHz ultrasound is limited by the structure and arrangement of the dental tissues. Therapeutic ultrasound has been used to treat a variety of dentally related ailments, and ultrasonic cleaning baths are used to clean both dental instruments and materials.     

Ultrasound assessment of skin and wound tissue: comparison with histology

Background/aims: Ultrasound is a valuable technique in dermatological assessment as it is non-invasive. This is particularly attractive for monitoring and evaluating wound healing. However, there is a limited literature on the use of ultrasound in monitoring wound healing. Methods: In this study, the structures of skin (human and porcine) and healing wounds (porcine) were visualised using ultrasound (20 MHz) and compared with histology from the same site. Measurements of various features were undertaken using both ultrasound and histometric techniques and the results from each compared. Hydroxyproline levels were also measured and correlated with ultrasound measurement of granulation tissue. Results: The echogenic characteristics of tissues are described. There was excellent correlation (r=0.96, P > 0.0001) between the ultrasound measurements and histology for porcine and human cadaver measurements. Ultrasound and histology measurements of acute porcine wounds also correlated well (r=0.96,P<0.0001). Comparison of hydroxyproline analysis with ultrasound measurements of fibrous granulation tissue (r=0.82,P > 0.001) indicates that ultrasound may be used to visualise accumulation of this tissue in wounds. Conclusions: Ultrasonography has been shown to be a useful, reliable, quantifiable technique for the assessment of wound healing.     

Bilateral endogenous Escherichia coli endophthalmitis: a devastating complication in an insulin-dependent diabetic.

We report a case of bilateral endogenous Escherichia coli endophthalmitis in an insulin-dependent diabetic. This condition appears to occur almost exclusively in diabetics, and is invariably related to a urinary tract infection. Treatment of any infection in diabetics should be aggressive, and any deterioration in vision should be addressed promptly.     

Trophic activity of Rabies G protein-pseudotyped equine infectious anemia viral vector mediated IGF-I motor neuron gene transfer in vitro

The present study examines gene delivery to cultured motor neurons (MNs) with the Rabies G protein (RabG)-pseudotyped lentiviral equine infectious anemia virus (RabG.EIAV) vector. RabG.EIAV-mediated beta-galactosidase (RabG.EIAV-LacZ) gene expression in cultured MNs plateaus 120 h after infection. The rate and percent of gene expression observed are titer-dependent (P < 0.001). The rat IGF-I cDNA sequence was then cloned into a RabG.EIAV vector (RabG.EIAV-IGF-I) and was shown to induce IGF-I expression in HEK 293 cells. MNs infected with RabG.EIAV-IGF-I demonstrate enhanced survival compared to MNs infected with RabG.EIAV-LacZ virus (P < 0.01). In addition, IGF-I expression in cultured MNs induced profound MN axonal elongation compared to control virus (P < 0.01). The enhanced motor neuron tropism of RabG.EIAV previously demonstrated in vivo, together with the trophic effects of RabG.EIAV-IGF-I MN gene expression may lend this vector to therapeutic application in motor neuron disease.     

Treatment of HIV infection in pregnant women: antiretroviral management options

Increasing rates of HIV infection in women worldwide, especially among those of childbearing age, reinforce the importance of understanding the management of HIV in pregnancy. Over the past decade, significant advances have been made in the prevention of vertical HIV transmission, including the use of single and combination antiretroviral therapy, elective caesarean section as the preferred mode of delivery and the elimination of breast feeding. Multiple clinical trials assessing antiretroviral therapy in pregnancy have been carried out worldwide. The first pivotal clinical trial, the AIDS Clinical Trials Group (ACTG) 076 study, was conducted in 1994 using a three-part zidovudine regimen. Despite the success of this regimen at decreasing rates of vertical transmission, it is not affordable in many developing countries. Consequently, many international clinical trials have concentrated on short-course antiretroviral regimens including zidovudine alone, zidovudine and lamivudine, and nevirapine alone. In the developed world, the management of nonpregnant HIV-infected individuals has also undergone significant advances and has implications for the management of HIV in pregnancy. A number of countries have participated in the development of guidelines for the management of HIV in pregnancy, which recommend that HIV-infected pregnant women should be offered combination antiretroviral therapy based on viral load and CD4+ cell count cut-offs used for individuals who are not pregnant, preferably with the inclusion of zidovudine. However, to maximise the benefits to their offspring, therapy is recommended at lower viral load thresholds than for nonpregnant adults. For antiretroviral-naive women, therapy is deferred until the second trimester because of the potential and uncertain risk of teratogenesis and the low risk of transmission during this period. Research has also found that maternal factors including viral load, immune status, chorioamnionitis, prematurely ruptured membranes and, to a lesser extent, intravenous drug use and smoking are associated with increased vertical transmission. These represent potentially modifiable risk factors that should be addressed before and throughout pregnancy. Despite the benefits of antiretroviral therapy to reduce HIV vertical transmission, its use can be complicated by known and unknown risks of toxicity to the mother, fetus or both as well as carrying the risk of developing drug-resistant virus. The latter can potentially compromise future treatment options for both the mother and child. Other important challenges include the use of antiretroviral drugs during pregnancy when the mother does not meet criteria for them for her own health, and balancing the relative risks and benefits of elective caesarean section at various degrees of viral load suppression. Clinicians managing HIV in pregnancy need to keep up to date with all the literature to provide optimal care, including counselling to allow mothers to balance the risks and benefits while deciding on treatment for both themselves and their children.