Three-dimensional histology vs. serial section histology in the treatment of primary basal cell carcinoma: a randomized, prospective, blinded study of 569 tumours.

BACKGROUND: For basal cell carcinoma (BCC), only few controlled data have been published so far, which directly compare micrographically controlled surgery with conventional serial section histology. In addition to Mohs surgery, which uses cryostat sections, also three-dimensional histology (3D-histology), based on paraffin sections, is available to ensure complete control of the margins and basic sections. OBJECTIVES: To investigate the rate of local recurrence (LR) as well as the number of required re-excisions for basal cell carcinomas with serial section histology vs. 3D-histology. METHODS: We compared serial sections histology with 3D-histology in a prospective, randomized, controlled blinded trial and analysed 569 BCC of all subtypes up to 30 mm diameter, 287 BCC in the 3D group and 282 BCC in the serial section group. Excisions were performed with adapted primary resection margin according to location and size of the tumour. Surgeons were blinded at the time of surgery as they did not know which histological method will be used. Both methods used paraffin sections. RESULTS: Both groups did not differ regarding patients age, tumour location, tumour diameter, tumour subtypes or primary resection margins. In the serial section group, re-excisions were required in 21%; 24 tumours (8.4%) recurred after a median of 2.2 years. In the 3D-histology group, re-excisions were required in 39%; 10 tumours recurred (3.5%) after a median of 2.8 years. The recurrence rates differed significantly between both groups. Mean follow-up was 4.5 years. CONCLUSIONS: 3D-histology is a useful technique to detect tumour outgrowths at the excision margins, but required a high rate of re-excisions. 3D-histology was associated with a significantly lower LR rate than serial section histology.

Transmission of SARS-CoV-2 in children aged 0 to 19 years in childcare facilities and schools after their reopening in May 2020, Baden-Württemberg, Germany.

We investigated data from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected 0-19 year olds, who attended schools/childcare facilities, to assess their role in SARS-CoV-2 transmission after these establishments' reopening in May 2020 in Baden-Württemberg, Germany. Child-to-child transmission in schools/childcare facilities appeared very uncommon. We anticipate that, with face mask use and frequent ventilation of rooms, transmission rates in schools/childcare facilities would remain low in the next term, even if classes' group sizes were increased.

Basal serum tryptase as risk assessment for severe Hymenoptera sting reactions in elderly.

BACKGROUND: Epidemiologic studies suggest that elderly people are more prone to develop severe anaphylactic reactions. However, the exact cause for this phenomenon remains unclear. AIMS OF THE STUDY: To study the role of the serum tryptase as a diagnostic parameter for individual risk evaluation and its impact on the severity of allergic reactions in elderly people. METHODS: Two hundred and seventy-four consecutive patients visiting the Department of Dermatology, Tübingen, Germany, who were diagnosed with honeybee or wasp venom allergy, were included in the study. RESULTS: Sting reaction severity increased with increased age and tryptase levels (P = 0.001 and P = 0.0003, respectively). Furthermore, we find not only a general increment in tryptase levels in elderly people (P = 0.0001) but also a continuous increase in tryptase concentrations even below the cut-off (11.4 microg/l) with increasing age (P = 0.0026). CONCLUSIONS: Our data confirm serum tryptase as a risk factor for severe anaphylactic reaction to hymenoptera stings. Furthermore, we give first evidence that basal serum tryptase levels increase continuously with age and being an indicator for either increased mast cell load or reactivity this can at least partly be responsible for the observed aggravated allergic reactions in elderly people. As those patients are at increased risk for life-threatening anaphylactic reactions, it should be considered to adjust VIT especially in elderly patients with elevated tryptase levels as recommended for patients with mastocytosis by increasing venom doses during VIT and by considering its life-long continuation.

Diagnostic value of nodule palpation in onchocerciasis.

Nodule palpation is the major diagnostic tool for determining the prevalence of infection in areas of the African Programme for Onchocerciasis Control (APOC) and is recommended for identifying communities at risk and selecting them for mass drug administration. The diagnostic value of palpation, however, has not been quantified in terms of sensitivity and predictive values. We derive these measures from the probability that a nodule is palpable, which has been estimated by stochastic simulations from an extensive pre-control database. We show that nodule palpation is only reliable in highly endemic areas and that false-positive diagnoses can lead to considerable misclassifications of regions where endemicity is actually low. Its diagnostic precision is poor because of large intra- and inter-individual variability. The findings underline the need for further development of available diagnostics that allow long-term monitoring when endemicity declines.

Assessment of Public Health and Economic Impact of Intranasal Live-Attenuated Influenza Vaccination of Children in France Using a Dynamic Transmission Model.

OBJECTIVES: We estimated the epidemiological and economic impact of extending the French influenza vaccination programme from at-risk/elderly (≥65 years) only to healthy children (2-17 years). METHODS: A deterministic, age-structured, dynamic transmission model was used to simulate the transmission of influenza in the French population, using the current vaccination coverage with trivalent inactivated vaccine (TIV) in at-risk/elderly individuals (current strategy) or gradually extending the vaccination to healthy children (aged 2-17 years) with intranasal, quadrivalent live-attenuated influenza vaccine (QLAIV) from current uptake up to 50% (evaluated strategy). Epidemiological, medical resource use and cost data were taken from international literature and country-specific information. The model was calibrated to the observed numbers of influenza-like illness visits/year. The 10-year number of symptomatic cases of confirmed influenza and direct medical costs ('all-payer') were calculated for the 0-17- (direct and indirect effects) and ≥18-year-old (indirect effect). The incremental cost-effectiveness ratio (ICER) was calculated for the total population, using a 4% discount rate/year. RESULTS: Assuming 2.3 million visits/year and 1960 deaths/year, the model calibration yielded an all-year average basic reproduction number (R 0) of 1.27. In the population aged 0-17 years, QLAIV prevented 865,000 influenza cases/year (58.4%), preventing 10-year direct medical expenses of €374 million. In those aged ≥18 years with unchanged TIV coverage, 1.2 million cases/year were averted (27.6%) via indirect effects (additionally prevented expenses, €457 million). On average, 613 influenza-related deaths were averted annually overall. The ICER was €18,001/life-year gained. The evaluated strategy had a 98% probability of being cost-effective at a €31,000/life-year gained threshold. CONCLUSIONS: The model demonstrated strong direct and indirect benefits of protecting healthy children against influenza with QLAIV on public health and economic outcomes in France.

High infection rates at low transmission potentials in West African onchocerciasis.

Onchocerciasis has been successfully controlled for many years in endemic countries but more than 120 million people are still at risk. Factors which stabilise the persistence of the parasite in the population must be studied to minimise the future risk of re-infection. Among these factors, the relationship between the annual transmission potential and the parasite establishment rate is a main determinant which has to date not been quantified. Using entomological information and palpation data collected by the Onchocerciasis Control Programme in West Africa prior to the initiation of control activities, we derive annual transmission potential-dependent estimates of the parasite establishment rate from statistical analyses and computer simulations. Even at very low transmission intensities, the filarial parasite Onchocerca volvulus can efficiently establish in the human population, originating from an infection process which is strongly limited with respect to the annual transmission potential. Implementing the estimates into a simplified transmission model predicts that the critical annual biting rate, below which transmission is not possible, is much lower than previously assumed. We conclude that under the current strategy of mass distribution of microfilaricides without additional measures of vector control, the risk of re-infection is higher than previously assumed.

Lipopolysaccharide-binding protein in noninfected neonates and those with suspected early-onset bacterial infection.

OBJECTIVES: To investigate postnatal lipopolysaccharide-binding protein (LBP) kinetics in term neonates and to test its diagnostic accuracy for early-onset bacterial infection (EOBI). STUDY DESIGN: A total of 99 neonates with clinical and serological signs of EOBI comprised the study group; 198 neonates with risk factors, but without EOBI, served as controls. LBP, C-reactive protein (CRP) and interleukin-8 (IL-8) were determined. RESULTS: LBP in the noninfected group increased until 24 h after birth (P < 0.05 vs 6 h). LBP and CRP correlated strongly in neonates with suspected EOBI (r = 0.63). Although LBP reached a higher sensitivity than CRP 6 and 12 h after clinical suspicion (45 (24-68) and 79% (54-94) vs 9 (0-24) and 39% (17-64); P < 0.05)), EOBI was most reliably detected by IL-8. CONCLUSION: LBP kinetics were age-dependent. LBP was not sufficiently sensitive in the prediction of EOBI.

Levels of luteinizing hormone, follicle-stimulating hormone, testosterone and dihydrotestosterone in the circulation of sexually maturing intact male rats and after orchidectomy and experimental bilateral cryptorchidism.

Plasma concentrations of LH, FSH, testosterone and dihydrotestosterone (DHT) have been measured in normal sexually maturing male rats from the age of 16-90 days. Between 16 and 25 days plasma testosterone levels were low, but rose suddenly on day 26. A similar increment occurred at the same time in plasma DHT levels, but this steroid reached its peak concentration later than testosterone. Plasma LH levels rose steadily from day 25 onwards, reaching their highest values on day 30. A marked increase in FSH levels was found on day 16, and a peak was reached on day 33 followed by a decline to a level characteristic of the adult. In addition, plasma levels of all these hormones were estimated in the male animals at various stages of development after orchidectomy and cryptorchidism. Four days after operation, the plasma levels of LH and FSH in the orchidectomized animals reached higher levels than those found in the intact animals, indicating the existence of a dynamic feedback relationship before puberty between gonadal steroids and pituitary gonadotrophic secretion. However, results from the experimental bilaterally cryptochid animals, suggested that the gonadal steriod-gonadotrophic feedback relationship could not be the only factor initiating puberty.

The relationships between the burden of adult parasites, host age and the microfilarial density in human onchocerciasis.

We investigate the relationship between the microfilarial density in the skin and the burden of adult female Onchocerca volvulus by analysing pre-control nodulectomy data which allow for a direct approach, independent of exposure. The data of 169 patients in Burkina Faso and 182 patients in Liberia represent savannah and forest onchocerciasis in West Africa, respectively. Whereas in Burkina Faso, a saturating relationship between microfilarial density and worm burden suggests the operation of density-dependent processes within human hosts, the Liberian data show a linear relationship implying no density dependence. The differences may derive from differences between both parasite strains, i.e. the savannah or the forest strain of O. volvulus. Consistently for both parasite strains and independent of the worm burden, the microfilarial density increases with host age emphasising the concept of the acquisition of immunological tolerance. In male hosts in Liberia, the microfilarial density increases stronger with the worm burden than in female hosts, whereas such sex-specific differences cannot be found in Burkina Faso. In the methodological part of this investigation, we suggest the beta-distribution to be most appropriate for describing variability in microfilarial densities and we present an approach to consider the uncertainty in the adult parasite burden which cannot be determined precisely in helminth infections. Implications of density dependence are discussed with respect to immunological processes in the human host and with respect to the success of control programs. The relationships described show that regulatory processes between the parasite and the human host are multi-dimensional, operating within a high degree of biological variability.

Certain batches of albumin solutions influence the expression of endothelial cell adhesion molecules.

OBJECTIVE: Increased levels of soluble adhesion molecules, a decreased PO2/FIO2 ratio and a tendency to worsened outcome have been reported following the use of human albumin in critical illness. The reasons are not yet understood. Since albumin solutions have previously been shown to contain proinflammatory mediators, a direct upregulation of adhesion molecules by contaminated batches may explain these findings. To examine this, we studied the effects of different albumin preparations on endothelial cell adhesion molecules in vitro. DESIGN: Experimental study. SETTING: Laboratory for cell biology. METHODS: Human umbilical venous endothelial cell cultures (n = 4) were incubated for 6 h at 5 mg/ml with four different human albumin solutions (HA1-4) from different manufacturers. Medium served as the control. Using flow cytometry, the effects on E-selectin, ICAM-1 and VCAM-1 expression were determined on unstimulated cells and on cells stimulated with tumour necrosis factor alpha at 0.5 ng/ml for 4 h. MEASUREMENTS AND RESULTS: On unstimulated cells, HA1 and HA4, two different batches from the same manufacturer, increased ICAM-1 by 22% and 15%, respectively. After stimulation, both solutions resulted in a 19% increased expression of E-Selectin. In addition, HA4 decreased VCAM-1 on stimulated cells (p < or = 0.05). Two albumin preparations from other manufacturers did not produce significant effects. CONCLUSIONS: Some albumin solutions directly modulate adhesion molecule expression on endothelial cells. This may, at least in part, explain the previous finding of increased soluble adhesion molecules and a decreased PO2/FIO2 ratio in critically ill patients undergoing volume replacement with human albumin.

C-fos protein expression in the nucleus of the solitary tract correlates with cholecystokinin dose injected and food intake in rats.

C-fos protein expression was investigated in the nucleus of the solitary tract (NTS) in response to increasing cholecystokinin (CCK) doses and food intake in rats by counting the number of c-fos protein positive cells in the NTS. C-fos protein expression in the NTS dose-dependently increased in response to CCK, the lowest effective dose being 0.1 microg/kg. The ED(50) for c-fos protein expression in the NTS in response to CCK was calculated to be 0.5 to 1.8 microg/kg, depending on the anatomical level of the NTS investigated. Food intake increased c-fos protein expression in the NTS, the maximum number of c-fos protein positive cells being reached at 90 min after the start of food intake. Regression analysis identified a positive correlation between c-fos protein expression and the amount of food intake. Our data indicate that subpopulations of the NTS that are activated by CCK or food intake are involved into the short-term regulation of food intake and the neural control of feeding by the caudal brainstem.

Genesis, sequestration and survival of Plasmodium falciparum gametocytes: parameter estimates from fitting a model to malariatherapy data.

Plasmodium falciparum malaria is one of mankind's main killers. Part of the parasite's life-cycle is spent in human blood, mainly as asexual stages. A fraction of the asexual parasites develops into gametocytes (gamete precursors) while sequestered in deep tissues. After re-entering the circulation, gametocytes can be picked up by a mosquito to continue the parasite's life-cycle. We present estimates of the conversion probability from asexual parasites to circulating gametocytes and of the gametocytes' sequestration and circulation times, obtained for the first time by fitting a dynamic model to individual patients' histories (daily records of 113 neurosyphilitic patients undergoing malariatherapy). The model assumes that the conversion probability can vary among the successive waves of asexual parasitaemia of a patient, and that gametocytes die at an age-dependent rate which increases under high asexual parasite densities. On average, 1 gametocyte per 156 asexual parasites (range 7.4-3700) is produced. The most remarkable findings are the large individual variation of conversion probabilities and circulation times, the average gametocyte circulation time of 6.4 days (range 1.3-22.2 days) which is more than twice the currently accepted value, and the large variation of conversion probabilities among successive waves of asexual parasitaemia without any particular time pattern. The latter finding could be explained by an association between conversion probability and variation of PfEMP1.

Density-dependent parasite establishment suggests infection-associated immunosuppression as an important mechanism for parasite density regulation in onchocerciasis.

The modulation of human immune response by filarial parasites has yielded contradictory experimental findings and attracted much controversy. We address the unresolved question of acquisition, establishment and accumulation of Onchocerca volvulus by using a modelling approach that relates computer simulations to cross-sectional data concerning parasite burdens in 913 West African onchocerciasis patients. It is shown that the acquisition of O. volvulus is not constant with host age; instead, the analysis of age profiles of parasite burdens strongly indicate the operation of immunosuppressive processes within the human host, associated with the presence of adult parasites or microfilariae. It is suggested that these processes suppress immunity against incoming infective larvae (L3), which themselves act as an immune modulating component once they have successfully overcome the barrier of concomitant immunity. Suppression of parasite-specific immunity leads to parasite establishment rates which increase along with the parasite burden, but which hardly depend on hyperendemic annual transmission potentials. Children, still immunocompetent due to low parasite burdens, acquire 0.1-0.5 adult female parasites per year, whereas older people, immunosuppressed due to high burdens, acquire 2-4 adult female parasites per year. Differences in parasite establishment between the forest and the savannah strains of O. volvulus are quantified and dynamic aspects of density-dependent parasite establishment discussed.

Deterministic models for the eradication of poliomyelitis: vaccination with the inactivated (IPV) and attenuated (OPV) polio virus vaccine.

Currently two polio vaccines, IPV and OPV, are in use which differ markedly in their epidemiological parameters. A simple epidemiological model in terms of ordinary differential equations is proposed to study the effects of vaccination campaigns using these vaccines. The numbers of interest are the reproduction number of the disease in the presence of vaccination and the critical vaccination coverage necessary to prevent an outbreak. For these numbers explicit representations are determined which can be used in comparing different vaccination strategies.

The influence of Emla cream on cutaneous microcirculation.

Emla cream is frequently used in surgical dermatology and in anesthesiology, for instance, during vascular surgery procedures. Because local anesthetics can have a vasoactive effect in addition to producing analgesia, we decided to document the effect of 5% Emla cream on cutaneous circulation in a prospective, placebo-controlled study. Skin circulation was monitored continuously under standardized conditions using video capillaroscopy, laser Doppler flowmetry and skin temperature. Recordings were made at the nailfold of the fourth finger (DIV) of the left hand of 12 volunteers with healthy veins over an observation period of 60 minutes under either Emla occlusive dressing or an occlusive dressing with placebo. Mean capillary red blood cell velocity changed only minimally under the Emla occlusive dressing, while placebo occlusive dressing led to a reduction of mean capillary red blood cell velocity from 0.21 mm/s to 0.12 mm/s (p<0.01). There was no statistically significant change of arterial capillary diameter under Emla or placebo occlusive dressing. Skin temperature dropped after 60 minutes of Emla cream occlusive dressing from an initial 26.7 to 24.0 degrees C (-10.1%; p<0.02). The same duration of placebo caused skin temperature to drop from 27.6 to 23.0 degrees C (-16.7%; p<0.001). Laser Doppler flux (543 nm) rose 13% with Emla (p=0.9) and dropped 41.9% under placebo occlusive dressing (p<0.03). Emla cream upregulated nutritive perfusion. No clinically relevant vasoconstrictive effects are expected from an application period of 60 minutes.

Giant sialolithiasis appearing as odontogenic infection.

The dentist frequently is called on to diagnose pathoses of the head and neck region. Two reports of giant submandibular sialoliths that were originally diagnosed as submandibular space odontogenic infections are presented. Careful history, and physical and radiographic examinations are necessary to assure proper diagnosis and treatment of this condition.

[A new optoelectronic measuring device for assessment of leg circumference in comparison with manual measurement]. / Ein neues optoelektronisches Messinstrument zur Erfassung von Beinumfängen im Vergleich zur manuellen Massbandmessung.

For compression treatment to be effective in patients with chronic venous insufficiency, it is vital that leg circumference be measured accurately. If compression stockings are custom fit and appropriate for the medical indications, patient compliance will be high. Exact measurements of circumference and length are prerequisites for a good fit. The aim of the present study was to compare an opto-electronic device for the contact-free measurement of calf circumference with the conventional manual method using a tape measure. We investigated the differences between the results obtained with the two methods, and also their reproducibility. Circumferences were measured at defined heights on an anatomically shaped non-yielding leg model and on the leg of a healthy volunteer by 10 different experimenters both with the tape measure and with the opto-electronic device. The calf circumferences measured manually with the tape measure varied significantly more than those measured opto-electronically, both in the leg model and in the leg of the volunteer. A systematic error in the opto-electronic method appears unlikely, since the manual measurements on the leg model were both larger and smaller than those obtained with the opto-electronic device. Reproducibility was exceptionally high with the opto-electronic device (standard deviation 0.11-0.42 cm). The opto-electronic method yields rapid accurate measurements of circumference with excellent intra- and inter-operator reproducibility.