Gonadal and uterine function in female survivors treated by chemotherapy, radiotherapy, and/or bone marrow transplantation for childhood malignant and non-malignant diseases.

OBJECTIVE: To evaluate gonadal function and uterine volume in a cohort of female survivors treated by chemotherapy, radiotherapy, and/or stem cell transplantation (SCT) for childhood malignant and non-malignant diseases. DESIGN: An observational study. SETTING: S. Matteo Hospital, Pavia, Italy. POPULATION: A cohort of 135 female survivors. METHODS: A clinical, hormonal, and ultrasonographic evaluation. Thirty-three patients (24%) had non-malignant haematologic diseases (thalassaemia or sickle cell anaemia), 68 (50%) had leukaemia, 23 (17%) had lymphomas, and 11 (8%) had solid tumours. In total, 106 patients had received SCT, preceded by a conditioning regimen. MAIN OUTCOME MEASURES: Anti-Müllerian hormone (AMH) and Inhibin-B, and uterine volume. RESULTS: The median concentrations of AMH and Inhibin-B in the entire cohort were 0.12 ng/ml (interquartile range, IQR, 0.1-0.5 ng/ml) and 3.5 pg/ml (IQR 0.1-13.2 pg/ml), respectively. In a stepwise ordered logistic regression analysis, conventional chemotherapy for the treatment of malignancies, as opposed to total body irradiation (TBI), was the only oncologically significant predictor of increased AMH levels (OR 4.8, 95% CI 1.9-12, P < 0.001). Conditioning treatment before or after menarche did not influence AMH concentrations (P = 0.24). The best predictor of reduced uterine volume was TBI during the preparation for the allograft (OR 3.5, 95% CI 1.4-8.4, P = 0.006). Increasing age at treatment (OR 0.86, 95% CI 0.77-0.95, P = 0.04), chemotherapy, as opposed to other treatments (OR 0.09, 95% CI 0.03-0.28, P < 0.001), and solid tumours as opposed to either leukaemia/lymphomas or non-malignant diseases (OR 0.2, 95% CI 0.07-0.56, P = 0.002) were associated with larger uterine volumes. CONCLUSIONS: Conditioning therapies for SCT, including TBI, had the worst effects on uterine volume and gonadal reserve. Increasing age at treatment and conventional chemotherapy were associated with less detrimental effects on uterine volume.

Effects of uncomplicated vaginal delivery and epidural analgesia on fetal arterial acid-base parameters at birth in gestational diabetes.

AIM: To investigate the effects of uncomplicated vaginal delivery and epidural analgesia on fetal acid-base parameters in women with gestational diabetes (GDM) compared with controls. METHODS: A retrospective case-control study of 142 women with gestational diabetes and 284 controls. To evaluate the effect of diabetes and analgesia on acid-base status correcting for potential confounders we used ordered logistic equations including quartiles of fetal arterial acid-base parameters collected at birth as outcomes and categories of diabetes and epidural analgesia as explanatory variables. RESULTS: In the GDM group cord base deficit (-2.63 mmol/l, interquartile range [IQR]=4.2 to -0.65 mmol/l vs. -1.9 mmol/l, IQR=-3.3 to -0.2 mmol/l, p=0.009, odds ratio (OR)=1.51, 95% confidence interval (CI)=1.04-2.18) was lower and concentration of calcium higher (1.49 mmol/l, IQR=1.42-1.56 mmol/l vs. 1.47 mmol/l, IQR=1.41-1.51 mmol/l, p=0.009, OR=1.69, 95% CI=1.12-2.56) compared with controls. Epidural analgesia in the GDM group was associated with reduced cord concentration of glucose (84.0mg/dl [4.7 mmol/l], IQR=70-103.3mg/dl vs. 92.5mg/dl [5.1 mmol/l], IQR=76.5-121.8 mg/dl, p=0.004), lactate (2.65 mmol/l (IQR=1.80-4.20) vs. 3.70 mmol/l (IQR=2.90-5.55 mmol/l), p=0.002) and less pronounced base deficit (-2.05 mmol/l, IQR=-3.90 to -0.17 mmol/l vs. -2.8, IQR=-5.57 to -1.05 mmol/l, p=0.01, OR=0.7, 95% CI=0.49-0.99). CONCLUSIONS: In uncomplicated pregnancies and deliveries, well-controlled gestational diabetes mellitus has potentially significant detrimental effects on fetal acid-base status at birth. Epidural analgesia reduces cord arterial glucose and lactates.

Histological and histomorphometric evaluation of immediate implant placement on a dog model with a new implant surface treatment.

PURPOSE: The aim of this study was to evaluate crestal bone resorption and bone apposition resulting from immediate post-extraction implants in the canine mandible, comparing a conditioned sandblasted acid-etched implant surface with a non-conditioned standard sandblasted implant surface. MATERIAL AND METHODS: In this experimental study, third and fourth premolars and distal roots of first molars were extracted bilaterally from six Beagle dog mandibles. Each side of the mandible received three assigned dental implants, with the conditioned surface (CS) on the right side and the non-conditioned surface (NCS) on the left. The dogs were sacrificed at 2 (n=2), 4 (n=2) and 12 weeks (n=2) after implant placement. RESULTS: The microscopic healing patterns at 2, 4 and 12 weeks for both implant types (CS and NCS) yielded similar qualitative bone findings. The mean crestal bone resorption was found to be greater for all implants with NCS (2.28+/-1.9 mm) than CS (1.21+/-1.05 mm) at 12 weeks. The mean percentage of newly formed bone in contact with implants was greater in implants CS (44.67+/-0.19%) than with the NCS (36,6+/-0.11%). There was less bone resorption with the CS than the NCS. CONCLUSION: The data show significantly more bone apposition (8% more) and less crestal bone resorption (1.07 mm) with the CS than with the NCS after 12 weeks of healing. This CS can reduce the healing period and increase bone apposition in immediate implant placements.

Laboratory control of oral anticoagulant treatment by the INR system in patients with the antiphospholipid syndrome and lupus anticoagulant. Results of a collaborative study involving nine commercial thromboplastins.

Because of the variable responsiveness of thromboplastins to lupus anticoagulants (LA), concerns have been raised about the validity of the prothrombin time-International Normalized Ratio (PT-INR) in monitoring oral anticoagulant treatment in patients with the antiphospholipid syndrome (APS) and LA. To date, few studies have been performed, numbers of patients investigated are relatively small and results are conflicting. We report on a multicentre study organized to investigate further this clinically relevant issue. Each of nine thrombosis centres was asked to collect plasma samples from patients with APS who were on oral anticoagulants (cases) and patients without APS who were on oral anticoagulants (controls). Nine thromboplastins (three human recombinant, one from human placenta and five from rabbit brain) were calibrated at the co-ordinating centre according to World Health Organization guidelines. Measurements of the INR and factor X amidolytic activity for all frozen plasmas were performed centrally. The numbers of patients investigated were 58 cases and 57 controls. Between-reagent variability of the INR was higher in cases [coefficient of variation (CV) = 12.4%] than in controls (CV = 6.7%), but this was because of one of the thromboplastins only (Thromborel R, human recombinant), which measured considerably higher INR values than the others in cases but not in controls. In conclusion, our data indicate that LA interference on the PT-INR measured with the majority of commercial thromboplastins is not enough to cause concern if insensitive thromboplastins, properly calibrated to assign them an instrument-specific International Sensitivity Index are used. New thromboplastins, especially those made of relipidated tissue factor, should be checked for their responsiveness to LA before they are used to monitor oral anticoagulant treatment in patients with APS.

An evaluation of the impact of training Honduran health care providers in interpersonal communication.

OBJECTIVE: To evaluate the impact of interpersonal communication (IPC) training on practice and patient satisfaction and to determine the acceptability of this training to providers in a developing country. DESIGN: The study used a pre-post design with treatment and control groups. Data collection methods included interaction analysis of audio-taped clinical encounters, patient exit interviews, and a self-administered questionnaire for health providers. STUDY PARTICIPANTS: Interaction analysis was based on an experimental group of 24 doctors and a control group of eight with multiple observations for each provider). Exit interviews were carried out with 220 pre-test patients and 218 post-test patients. All 87 health providers who received training responded to the self-administered questionnaire. INTERVENTION: A brief in-service training programme on interpersonal communications was presented in three half-day sessions; these focused on overall socio-emotional communication, problem solving skills and counselling. MAIN OUTCOME MEASURES AND RESULTS: The IPC intervention was associated with more communication by trained providers (mean scores of 136.6 versus 94.4; P = 0.001), more positive talk (15.93 versus 7.99; P = 0.001), less negative talk (0.11 versus 0.59; P = 0.018), more emotional talk (15.7 versus 5.5; P = 0.021), and more medical counselling (17.3 versus 11.3; P = 0.026). Patients responded by communicating more (mean scores of 113.8 versus 79.6; P = 0.011) and disclosing more medical information (54.7 versus 41.7; P = 0.002). Patient satisfaction ratings were higher for providers who had received the training and providers reported training to be relevant and useful. CONCLUSIONS: Further validation of IPC skills and simplification of assessment methods are needed if IPC is to be an area for routine monitoring and quality improvement.

The effects of a continuing medical education programme in interpersonal communication skills on doctor practice and patient satisfaction in Trinidad and Tobago.

This study investigates the effects of a brief training programme on the communication skills of doctors in ambulatory care settings in Trinidad and Tobago. Evaluation of doctor performance is based on analysis of audiotapes of doctors with their patients during routine clinic visits and on patient satisfaction ratings. A pre-test/post-test quasi-experimental study design was used to evaluate the effects of exposure to the training programme. Doctors were assigned to groups based on voluntary participation in the programme. Audiotapes of the 15 participating doctors (nine trained and six control) with 75 patients at baseline and 71 patients at the post-training assessment were used in this analysis. The audiotapes were content-coded using the Roter Interaction Analysis System (RIAS). Doctors trained in communication skills used significantly more target skills post-training than their untrained colleagues. Trained doctors used more facilitations in their visits and more open-ended questions than other doctors. There was also a trend towards more emotional talk, and more close-ended questions. Patients of trained doctors talked more overall, gave more information to their doctors and tended to use more positive talk compared to other patients. Trained doctors were judged as sounding more interested and friendly, while patients of trained doctors were judged as sounding more dominant, responsive and friendly than patients of untrained doctors. Consistent with these communication differences, patient satisfaction tended to be higher in visits of trained doctors.

Congenital resistance to activated protein C in patients with lupus anticoagulants: evaluation of two functional assays.

The R506Q mutation ("Factor V Leiden") is responsible for the resistance to activated Protein C (aPCR), that is evaluated by coagulation tests. Such tests cannot be used in patients with lupus anticoagulants (LAs), due to the interfering effect exerted by these antibodies on "in vitro" phospholipid-dependent coagulation tests. For this reason, assays have been developed to evaluate aPCR that are insensitive to the presence of LA antibodies. We evaluated two such coagulation tests in the plasma of 82 consecutive patients with LAs. By polymerase chain reaction 3 patients (3.6%) were found heterozygous for the R506Q mutation. aPCR was evaluated by two clotting assays, proposed to be "insensitive" to the presence of LAs: 1. aPCR-tissue factor-based assay, using Factor V deficient plasma and 1:40 diluted test plasma; 2. aPCR-dRVVT-based assay with highly concentrated phospholipids. Their interassay coefficient of variation was 28% and 6.2%, respectively. Compared to the polymerase chain reaction analysis, the 2 tests displayed the following characteristics: sensitivity 67% vs 100%, specificity 92% vs 96%, positive predictive value 25% vs 50%, negative predictive value 99% vs 100%. respectively. Among LA patients without the R506Q mutation, 5 scored positive in the aPCR-tissue factor-based assay, 2 in the aPCR-dRVVT-based assay and another one in both assays. Our findings suggest that the aPCR-dRVVT-based test is more reliable and sensitive than the aPCR-tissue factor-based one to the R506Q mutation in patients with LAs. Both assays, when negative, make unlikely the presence of the R506Q mutation. Polymerase chain reaction analysis remains, however, to be performed when either test is positive.

Assessment of the influence of citrate concentration on the International Normalized Ratio (INR) determined with twelve reagent-instrument combinations.

Citrate concentration is one of the variables that can affect coagulation tests. However, few studies have so far been performed to assess the magnitude of this effect on coagulation tests in general and PT in particular. The aim of this study was to assess the extent of influence of citrate concentration on the PT test with results expressed as INR. Twelve reagent-instrument combinations (systems) were calibrated vs. the Reference Preparation BCT/441 using plasmas collected in either 105 mM or 129 mM citrate from normals and anticoagulated patients (OAT). PTs for plasmas collected in 129 mM citrate were longer than those collected in 105 mM both for normals and patients on OAT, but the ratios (patient-to-normal clotting times) for the two citrate concentrations were significantly different in many instances, implying that the International Sensitivity Index (ISI) is also different. ISIs for calibrations with plasmas collected in 105 mM were greater (up to 10%) than those with plasmas collected in 129 mM citrate. When PT ratios were transformed into INR using crossover ISIs (i.e., plasmas collected in 105 mM and ISI determined with plasmas collected in 129 mM citrate, or vice versa) we found that an INR of 4.5 could be up to 20% apart from the value that would have been obtained if the appropriate ISI was used. Moreover, if the ISI determined with the manual technique was used to convert PTs obtained with a particular instrument into INR, the effect of citrate concentration was even greater (INR difference up to 64%). Should these observations be valid for other systems, they might provide additional explanations for the frequent reports which document discrepancies in the INR determined with different systems to which incorrect ISI might have been applied. World-wide consensus on a single citrate concentration to collect patients' as well as lyophilized plasmas to be used in External Quality Assessment Schemes and for local system calibration is therefore urgently needed.

Standardization of the APC resistance test. Effects of normalization of results by means of pooled normal plasma.

Results for APC resistance tests are expressed as the ratio of the clotting time with and without APC (APC ratio). Normalization by dividing the patient's APC ratio by that of the pooled normal plasma (PNP) (n-APC ratio) was proposed to minimize between-lot reagent variability. To evaluate the merits of different expressions of the results, sets of 80 coded frozen plasmas from carriers (n = 30), non-carriers (n = 30) of the FV:Q506 mutation and 10 copies each of two control plasmas were sent to 7 expert laboratories which were asked to assess APC resistance by their methods. Results were expressed as APC ratio and n-APC ratio by the local PNP and 2 common PNP (A and B). These contained plasmas from the same (n = 20) non-carriers. In PNP A, plasma from one non-carrier was replaced with that from one heterozygous carrier. The merits of different expression of results were judged by (i) within-laboratory reproducibility: (ii) discrimination of carriers from non-carriers: (iii) between-method comparability of results. The influence of FV:Q506 plasma in the preparation of PNP was also assessed. Reproducibility, generally good even with results expressed as APC ratio (median CV 4.6% and 3.0% for normal and abnormal control), was not changed by normalization. Discrimination did not change whatever the method of result expression. Between-method comparability of results was scarcely affected by normalization with the local PNP, whereas it was considerably improved after normalization with the common PNP, but only for the non-carriers. APC ratios for PNP A by all methods were significantly lower than those for PNP B. Thus, the presence of mutant FV in a proportion as low as 2.5% may reduce the APC ratio of the PNP.

International collaborative study for the calibration of a proposed reference preparation for thromboplastin, human recombinant, plain. On behalf of the Subcommittee on Control of Anticoagulation.

Stocks of the International Reference Preparation (IRP) for thromboplastin, human, plain, coded BCT/253 and held by the World Health Organization (WHO) are nearly exhausted and must be replaced. For practical reasons the choice of the replacement candidate was restricted to two available human recombinant preparations which were coded as X/95 and Y/95 and calibrated in an international collaborative study involving 19 laboratories from Europe, Australia, Canada and Argentina. To minimize the differences between routes of calibration, the two candidates were calibrated against the existing WHO-IRP from human, rabbit and bovine origin and the final ISI was the resultant average value. On the basis of predefined criteria (i.e., within- and between-laboratory precision of the calibration and the conformity to the calibration model), X/95 was the preferred candidate. The assigned ISI (SE of the mean) value is 0.940 (0.0060) and the interlaboratory coefficient of variation 4.7%.

Determination of the International Sensitivity Index of a new near-patient testing device to monitor oral anticoagulant therapy--overview of the assessment of conformity to the calibration model.

A key issue for the reliable use of new devices for the laboratory control of oral anticoagulant therapy with the INR is their conformity to the calibration model. In the past, their adequacy has mostly been assessed empirically without reference to the calibration model and the use of International Reference Preparations (IRP) for thromboplastin. In this study we reviewed the requirements to be fulfilled and applied them to the calibration of a new near-patient testing device (TAS, Cardiovascular Diagnostics) which uses thromboplastin-containing test cards for determination of the INR. On each of 10 working days citrated whole blood and plasma samples were obtained from 2 healthy subjects and 6 patients on oral anticoagulants. PT testing on whole blood and plasma was done with the TAS and parallel testing for plasma by the manual technique with the IRP CRM 149S. Conformity to the calibration model was judged satisfactory if the following requirements were met: (i) there was a linear relationship between paired log-PTs (TAS vs CRM 149S); (ii) the regression line drawn through patients data points, passed through those of normals; (iii) the precision of the calibration expressed as the CV of the slope was <3%. A good linear relationship was observed for calibration plots for plasma and whole blood (r = 0.98). Regression lines drawn through patients data points, passed through those of normals. The CVs of the slope were in both cases 2.2% and the ISIs were 0.965 and 1.000 for whole blood and plasma. In conclusion, our study shows that near-patient testing devices can be considered reliable tools to measure INR in patients on oral anticoagulants and provides guidelines for their evaluation.

Screening for the FV:Q506 mutation--evaluation of thirteen plasma-based methods for their diagnostic efficacy in comparison with DNA analysis.

The factor V (FV) mutation Q506 that causes resistance to activated protein C (APC) is the genetic defect associated most frequently with venous thrombosis. The laboratory diagnosis can be made by DNA analysis or by clotting tests that measure the degree of prolongation of plasma clotting time upon addition of APC. Home-made and commercial methods are available but no comparative evaluation of their diagnostic efficacy has so far been reported. Eighty frozen coded plasma samples from carriers and non-carriers of the FV:Q506 mutation, diagnosed by DNA analysis, were sent to 8 experienced laboratories that were asked to analyze these samples in blind with their own APC resistance tests. The APTT methods were highly variable in their capacity to discriminate between carriers and non-carriers but this capacity increased dramatically when samples were diluted with FV-deficient plasma before analysis, bringing the sensitivity and specificity of these tests to 100%. The best discrimination was obtained with methods in which fibrin formation is triggered by the addition of activated factor X or Russell viper venom. In conclusion, this study provides evidence that some coagulation tests are able to distinguish carriers of the FV:Q506 mutation from non-carriers as well as the DNA test. They are inexpensive and easy to perform. Their use in large-scale clinical trials should be of help to determine the medical and economic benefits of screening healthy individuals for the mutation before they are exposed to such risk factors for venous thrombosis as surgery, pregnancy and oral contraceptives.

Aberrant expression of epidermal growth factor receptor in aural cholesteatoma.

A monoclonal antibody recognizing an epitope of the external domain of the human epidermal growth factor (EGF) receptor was used in an alkaline phosphatase-antialkaline phosphatase (APAAP) technique to compare the distribution of this protein in normal human skin and aural cholesteatoma. EGF receptors appear to be highly expressed on the basal layer of the epidermis, in hair follicle apocrine sweat glands, and in the capillary system of normal skin. Cholesteatoma epithelium showed increased positive reactions in the suprabasal layers. A heterogeneity in the expression was found in different parts of the cholesteatoma. These results suggest the presence of an aberrant regulation and persistence of EGF receptors in cholesteatoma and confirm the hyperproliferative character of the cholesteatoma epithelium.

Possible role of interleukin 1 alpha and interleukin 1 beta in the pathogenesis of cholesteatoma of the middle ear.

Cholesteatoma of the middle ear is characterized by the presence of hyperproliferative keratinizing squamous epithelium in the middle ear cavity and destruction of adjacent bone. Interleukin 1 (IL-1) is an autocrine growth factor for normal keratinocytes and is capable of inducing bone degradation. The distribution of two molecular species of IL-1, IL-1 alpha and IL-1 beta, was investigated immunohistochemically in the hyperproliferative epithelium of cholesteatoma, in normal epidermis of the auditory canal and of the retroauricular region, and in nonkeratinizing tonsillar epithelium. In all squamous epithelia examined, IL-1 alpha and IL-1 beta were present in comparable amounts. The IL-1 content of cholesteatoma epithelium was clearly increased in relation to normal skin keratinocytes. All cellular layers of cholesteatoma epithelium stained strongly and uniformly for Il-1 alpha and IL-1 beta, whereas the keratin layer was negative for IL-1. No particularly strong reaction with basal cells was detected. In the connective tissue under the squamous epithelium of cholesteatoma, intensely positive cells were scattered between negative stromal cells. Our results suggest that IL-1 could be liberated from disintegrating keratinocytes and cells of the monocyte-macrophage lineage, stimulate the proliferation of the cholesteatoma epithelium in an autocrine manner, and contribute to the enhancement of bone destruction in the presence of cholesteatoma.

[Interleukin-1-containing cells in cholesteatoma of the middle ear]. / Interleukin 1-enthaltende Zellen im Cholesteatom des Mittelohres.

Cholesteatoma of the middle ear and the adjacent temporal bone consists of hyperproliferative keratinizing squamous epithelium in the middle ear cavity, and is capable of destroying the bone. Interleukin-1 (IL-1), an autocrine growth factor for epithelial keratinocytes, is characterized by its capacity to initiate bone absorption. Using immunohistochemical methods, the distribution of two different species of interleukin, IL-1 alpha and IL-1 beta, in cholesteatoma tissue (Fig. 2), the skin of the external ear canal, and the retroauricular region was investigated (Fig. 1). Comparable amounts of both IL-1-species were found in all squamous epithelia examined, but interleukin in cholesteatoma epithelium was increased in comparison with normal epidermis. All cellular layers stained uniformly and equally strongly for IL-1 alpha and IL-1 beta, whereas the dead cells of the keratin layer were negative for both. Some intensely stained cells were found scattered in the connective tissue underlying the basal layer of the cholesteatoma (Fig 4). Using double staining techniques these cells were shown to be mainly macrophages (Fig 6). Our results suggest that IL-1 could be liberated from disintegrating keratinocytes and cells of the monocyte-/macrophage lineage, and stimulate the proliferation of the cholesteatoma epithelium in an autocrine manner, thus contributing to the increased bone destruction seen in cholesteatoma.

Immunotype findings in macrophages in aural cholesteatomas.

Since a heavy cellular infiltrate is seen in the stroma of most aural cholesteatomas, we attempted to characterize this cell population in more detail using monocyte/macrophage-specific monoclonal antibodies. KiM1 + (specific for CD11c antigen, the 150 kDa alpha-chain of a leukocyte integrin), and KiM6+ phagocytes were present in two- or fourfold higher numbers in the stroma of the six excised cholesteatomas than in the control tissues. Since the stroma of the cholesteatoma is devoid of microvessels, the typical perivascular localization of dermal macrophages was not seen in the cholesteatomas studied. The density of the macrophages in the normal ear skin was much higher in the upper dermis than in the lower dermis. In the cholesteatomatous specimens, the phagocytes were evenly scattered within the connective tissue and the cellular infiltrate. In contrast to diseased skin, no Mac 387+ macrophages were detected in the cholesteatomas. A great number of phagocytic cells closely resembling dermal macrophages was found in the stroma of the cholesteatomas and probably contributes to an active autoimmune process.

Immunologically activated cells in aural cholesteatoma.

In this immunohistochemical study, we characterized the cells infiltrating the stroma of acquired aural cholesteatomas in detail, using a panel of monoclonal antibodies directed against immune cell type-specific antigens, HLA class II antigens, and interleukin-2 receptor. For all antibodies used, normal ear skin was stained for comparison. The vast majority of the infiltrating cells was CD45-positive, ie, derived from bone marrow. Reactivity with anti-CD3 and anti-CD6 antibodies revealed an abundant infiltration of T lymphocytes beneath the squamous epithelium of cholesteatoma. The B lymphocyte-specific anti-CD19 and anti-CD22 antibodies detected only occasional positive cells. Hence, the cellular infiltrate in the stroma of aural cholesteatoma is made up primarily of T cells with macrophages scattered between them. Expression of HLA-DR was almost as high as that of CD45, whereas CD25-positive cells were detected in lower amounts. We infer that the majority of T cells and macrophages in the stroma of cholesteatoma are in an immunologically activated state. The characteristics of the infiltrating cell population suggest an antigen-driven process in cholesteatoma.

[Noise-induced hearing loss and tinnitus]. / Lärmschwerhörigkeit und Tinnitus.

The presence of subjective tinnitus is an important aspect in the evaluation of hearing loss induced by noise. Tinnitus due to this condition is characterised by a frequency of 3,000 Hz or above and is closely related to the frequency range of maximal hearing loss. Tinnitus below 1,000 Hz is not induced by noise, and indicates the presence of a different cause for the hearing loss. This type of tinnitus should not be regarded as an occupational disease: it requires extensive investigation.

[Cutaneous leishmaniasis of the ear muscle. A case report]. / Die kutane Leishmaniose der Ohrmuschel. Ein Fallbericht.

Cutaneous leishmaniasis is a parasitic infection which is especially endemic in the southern parts of Europe, in several regions of Africa, and in South and Central America. Whether treatment is necessary or not depends on the virulence of the germ, the infection's localization, and the host's immunological reaction. Because of the high rate of recidivation and the large number of undesirable side-effects of systemic chemotherapy of localized cutaneous leishmaniasis, several methods of local therapy have been tested. This case report demonstrates one of several approaches to the local treatment of this disease. Despite progress in this field, cutaneous leishmaniasis will continue to be a considerable medical and sociopolitical problem, because successful treatments in under-developed countries must be highly efficient, cost little, be easy to administer, and have a low rate of undesirable side-effects.