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We describe the case of a 54-year old woman with breast cancer who was treated by vancomycin for febrile neutropenia due to a methicillin-resistant Staphyloccocus epidermidis infection of a surgically implanted catheter. She developed an hypersensitivity reaction to vancomycin associating neutropenia, fever, skin rash and elevated liver enzymes following re-challenge with vancomycin after having been misdiagnosed with septic thrombophlebitis. Following this re-challenge, neutrophils count fell dramatically but promptly resolved after cessation of vancomycin.

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BACKGROUND: The development of systemic and/or cutaneous granulomas associated with immunodeficiency is well established, particularly with common variable immunodeficiency (CVID). We report the case of an immunocompromised child presenting with cutaneous granulomas, predominantly on the face. PATIENTS AND METHODS: A boy aged 6 years and 9 months presenting complex and incompletely defined immunodeficiency presented with gradually worsening cutaneous lesions of granulomatous aspect on his face and right foot. Extensive laboratory tests showed no infectious or neoplastic processes. Biopsies of the lesions confirmed the presence of granulomas. Systemic corticosteroids produced no satisfying improvement and were changed to anti-TNFα. The lesions had completely disappeared after 6 months. Treatment was continued for 6 months, with no relapse 6 months after discontinuation. CONCLUSION: The originality of our case lies in the presentation of cutaneous granulomas, appearing in the context of an undefined immunodeficiency other than CVID, as well as in the therapeutic aspect, with the successful use of biotherapies in such a clinical setting.

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The purpose of this investigation was to examine the influence of an acute bout of resistance exercise (RE) on intramuscular triglyceride (IMTG) and muscle glycogen concentrations and intracellular signaling in women with high body fat content. Six overweight women with a high percent body fat (age 29+/-3 yr; BMI 28+/-3 kg/m(2), body fat 38+/-4%) performed 6 sets of 10 repetitions of knee extension exercise at 70% 1RM. Muscle biopsies were obtained from the vastus lateralis before, 1 min after (POST1), and 2 h after (POST2) exercise. Acute RE reduced (p<0.05) IMTG content approximately 40% at POST1 and POST2 (75+/-5; 45+/-6; 50+/-10 mmol/kg/dry wt). Muscle glycogen was also reduced (p<0.05) approximately 25% at POST1 and remained lower at POST2 (317+/-14; 241+/-30; 235+/-26 mmol/kg/dry wt). ERK1/2, SAPK/JNK, and p38 phosphorylation were increased (p<0.05) approximately 2-3-fold at POST1 and ERK1/2 remained elevated and POST2 whereas SAPK/JNK and p38 returned to basal levels. AMPKalpha phosphorylation was unchanged in response to RE. These results show that both IMTG and muscle glycogen stores serve as an important energy source during RE in overweight women and the MAP kinase signaling response to RE is not compromised by high levels of body fat.

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The epidermal growth factor receptor (EGFR) is overexpressed in many solid tumors. Its inactivation has an inhibitory effect on the growth and spread of the tumoral cells. It therefore represents an attractive target to treat different cancers. Several molecules have already been registered while others are still under evaluation. One of the common side effects of these therapies is the development of cutaneous toxicities, more precisely a cutaneous rash, sometimes major and distressing. The physiopathology of these cutaneous side effects is poorly understood. Moreover a correlation between the severity of the rash and the tumoral response has been demonstrated in some studies. If this link is confirmed, the rash could be used as a marker for the anti-tumoral activity. This review will summarize the clinical presentations and the current recommendations for the management of cutaneous toxicities induced by EGFR inhibitors.

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BACKGROUND: Stage IV melanoma has a poor prognosis with a median survival of 3-11 months from diagnosis of distant metastases. Response rates in first-line regimens range around 15-20%. Non-responders have a median survival around 6 months. Currently, no second-line treatment in advanced melanoma has been established. PATIENTS AND METHODS: In a clinical phase II study we evaluated the efficacy of liposomal doxorubicin (Caelyx) in 30 patients (17 m, 13 f) with progressing metastatic melanoma who had failed a previous chemotherapy. Liposomal doxorubicin was given in an outpatient setting at a dose of 50 mg/m2 i.v. on d1, d22, d43 and d64, subsequently at 40 mg/m2 at d85 before first staging and in 4-week intervals thereafter. Treatment was very well tolerated with 100 cycles given in total. Response rate, survival time, time-to-progression and toxicity were assessed. RESULTS: Erythrodysesthesia was the most severe toxicity in 6% at CTC grade 3. Liposomal doxorubicin was of limited clinical efficacy with 21 patients progressing within the first 12 weeks. However, 7 patients were treated 3-9 months and were stable for >90 days, achieving 5 SD, 1 PR and 1 CR. Median survival after initiation of second-line treatment was 214 days (95% CI: 151-304 days) with 7 patients surviving >300 and 5 patients >400 days. CONCLUSIONS: Liposomal doxorubin as monotherapy is well tolerated but of limited clinical efficacy. Whether the survival benefit of a significant proportion of patients (20%) holds true in larger cohorts and whether the efficacy of liposomal doxorubicin can be improved by combinations without compromising the low toxicity profile needs further studies.

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BACKGROUND: We present the case of a patient with malignant melanoma stage IV according to the American Joint Committee on Cancer (AJCC) classification and an unusual pattern of metastasis to the mucosa of the esophagus, the stomach, the bladder and the palatine tonsil. CASE REPORT: A 38-year-old male patient with metastatic malignant melanoma of stage III (AJCC) was admitted for initiation of adjuvant therapy. 4 months earlier a primary melanoma of the left upper leg had been excised and 2 months later the patient had undergone a left inguinal lymph node dissection revealing 2 metastatic lymph nodes. On admission the patient complained of a sore throat and right cervical lymphadenopathy. He underwent a tonsillectomy and a lymphadenectomy which both revealed melanoma metastases. A PET scan using F-18-fluorodeoxyglucose (FDG) showed focal metabolic activity in the middle mediastinum. Two cycles of dacarbazine (DTIC) chemotherapy were performed during which the patient developed cutaneous metastases, dyspepsia, and mild hematemesis. Gastroscopy revealed bleeding from mucosal metastases of the esophagus and stomach. A few weeks later the patient developed macroscopic hematuria. A cystoscopy was performed and showed metastases to the mucosa of the bladder. Nutrient vessels of these bladder metastases were embolized in order to control bleeding. The patient is currently alive with progressive disease. RESULTS: This case presents common and uncommon sites of metastatic melanoma to the mucosa with the typical clinical manifestations in a single patient.

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Special research work has taught that general practice (family medicine) is a specialization of its own. It requires specific education and vocational training. As far as universities and administrative bodies have accepted it no doctor can start practising family medicine unless he has passed a vocational training of many years duration. That fact together with a successful continued research concerning applied general practice should initiate a true renaissance of general practice.

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We describe a simple method to assign a diagnosis of cataract to patients with obscurely impaired vision as well as to those with mild lens opacities. When the narrowest slit is used in a slitlamp examination, a small beam of light appears on the macula. Routine fundoscopy with the 78.0 diopter lens or a 3-mirror glass is appropriate. If a cataract is present, the beam of light is scattered into several straight lines, distorted lines, or both. This has proved a useful diagnostic tool when the lens appears clear but the patient's vision is impaired, and extensive examinations such as computer tomography or nuclear magnetic resonance tomography for impaired vision may be avoided. The beam-deflection method uses devices that are generally available and can detect cataract in the early stages of development.

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The trial to find connections between the frequency of cases in general medicine and life expectancy of the population succeeded, concerning superficial pyogenic infections by meta-analysing cases-statistics 1944-1996. More could be found by special, prospective, well-planned, comparable statistics of long duration, although it is unlikely that such expensive and difficult investigations will ever be made.

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Clinical specialists are not yet exploring the vast field of medicine applied by them. As a consequence, clinical medicine is in need of suitable names for many results of consultations. The concept "diagnosis" has become insignificant in specialists' medicine. Only specific basic research can alter this disturbed balance between clinical science and practice.

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One aim of applied medicine is to uncover, as early as possible, avoidably dangerous courses of diseases. All attempts to install obligatory investigations for the early detection of certain malignancies in general practice have failed for various reasons. The success rate for detecting life-threatening diseases in general practice could be rather high, if all the new tools, developed by basic specific research, were applied.

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OBJECTIVE: To examine the clinical efficacy of mifepristone 600 mg followed on the same day or two days later by misoprostol 400 microg orally in women undergoing medical termination of pregnancy whose pregnancies have a gestational age up to 49 days. DESIGN: Prospective, randomised trial. SETTING: Clinical research office. PARTICIPANTS: Eighty-six women, requesting elective termination of a pregnancy which has a gestational age of < or = 49 days. METHODS: After administration of mifepristone 600 mg, participants were randomised to take misoprostol six to eight hours later (Group 1) or 48 hours later (Group 2). Women returned for a follow up evaluation 24 +/- 1 hours after taking the misoprostol. Participants in Group 1 who had not aborted received a second dose of misoprostol to take 48 hours after the mifepristone. All women returned approximately two weeks after receiving mifepristone. If termination of pregnancy had still not occurred and the pregnancy was non-viable, the woman returned again in three weeks. MAIN OUTCOME MEASURES: Rate of complete abortion 24 hours after administration of misoprostol. RESULTS: At 24 hours after receiving misoprostol, 21/42 (50%, 95% CI 35%, 65%) women in Group I and 40/44 (91%, 95% CI 82%, 99%) women in Group 2 had complete abortions. By follow up two weeks later after the administration of mifepristone, 40/42 (95%, 95% CI 89%, 100%) women in Group 1 and 43/44 (98%, 95% CI 93%, 99%) women in Group 2 were known to have complete abortions. Nausea, vomiting or diarrhoea in women using the standard regimen (Group 2) occurred in 68%, 36%, and 20%, respectively. CONCLUSIONS: After treatment with mifepristone 600 mg, administration of misoprostol 400 microg orally on the same day is not as effective at causing abortion within the first 24 hours compared with the standard time interval of 48 hours between medications.

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Heterochrony, evolutionary changes in rate or timing of development producing parallelism between ontogeny and phylogeny, is viewed as the most common type of evolutionary change in development. Alternative hypotheses such as heterotopy, evolutionary change in the spatial patterning of development, are rarely entertained. We examine the evidence for heterochrony and heterotopy in the evolution of body shape in two clades of piranhas. One of these is the sole case of heterochrony previously reported in the group; the others were previously interpreted as cases of heterotopy. To compare ontogenies of shape, we computed ontogenetic trajectories of shape by multivariate regression of geometric shape variables (i.e., partial warp scores and shape coordinates) on centroid size. Rates of development relative to developmental age and angles between the trajectories were compared statistically. We found a significant difference in developmental rate between species of Serrasalmus, suggesting that heterochrony is a partial explanation for the evolution of body shape, but we also found a significant difference between their ontogenetic transformations; the direction of the difference between them suggests that heterotopy also plays a role in this group. In Pygocentrus we found no difference in developmental rate among species, but we did find a difference in the ontogenies, suggesting that heterotopy, but not heterochrony, is the developmental basis for shape diversification in this group. The prevalence of heterotopy as a source of evolutionary novelty remains largely unexplored and will not become clear until the search for developmental explanations looks beyond heterochrony.

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This investigation examined the effects of 4 weeks of non-dominant arm unloading on the functional and structural characteristics of the triceps brachii muscle of six normo-active college-age males (age: 23 +/- 1 years, height: 176 +/- 4 cm, weight: 76 +/- 6 kg). The primary intention of this study was to determine if arm unloading is an effective analogue for simulating the effects of weightlessness on human skeletal muscle. Subjects were tested 2-3 days preceding unloading in a standard arm sling and following removal of the sling. The sling was worn during waking hours to unload the arm. Subjects were allowed to remove the sling during sleep and bathing. Torque production (Nm) during maximal isometric extension at 90 degrees significantly declined (P < 0.05) in response to unloading (53.93 +/- 5.07 to 47.90 +/- 5.92; 12%). There was no significant change (P > 0.05) in the force-velocity attributes of the triceps over the other measured velocities (1.05, 1.57, 2.09, 3.14, 4.19, 5.24 rad.s-1). Cross-sectional muscle area (CSA) of the upper arm was smaller (44.3 +/- 2.7 to 42.4 +/- 2.5 cm2; 4%) following 4 weeks of unloading (P < 0.05). Histochemical analysis of individual muscle fibres demonstrated reductions in fibre CSA of 27 and 18% for type I and type II fibres, respectively. However, these changes were not statistically significant. Electrophoretic analysis of muscle samples revealed a significant increase (40 +/- 7 to 58 +/- 4%, pre- and post-, respectively) in myosin heavy chain (MHC) type II isoforms following unloading. Reductions in type I MHC isoform composition failed to reach statistical significance (P < 0.08). Amplitude of the integrated electromyographic (IEMG) signal during maximal isometric contraction of the long head of the triceps decreased by 21% in response to the 4-week unloading period (P < 0.05). The changes in triceps, muscle structure and function found with arm unloading are similar in magnitude and direction to data obtained from humans following exposure to real and simulated weightlessness. These findings demonstrate that arm unloading produces some of the effects seen in response to weightlessness in muscles of the upper arm and provides potential for an additional model to simulate the effects of microgravity on human skeletal muscle.

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Keratinocyte activation comprises changes in protein and gene expression pattern resulting in phenotypic and functional changes necessary for re-epithelialization such as the expression of urokinase-type plasminogen activator (uPA) and its cell surface receptor (uPA-R; CD87). As uPA and uPA-R are rapidly induced after dispase-mediated detachment of cultured normal human epidermal keratinocytes (NHEK) we hypothesized that dispase-mediated detachment may cause a similar "activation" of keratinocytes with uPA and uPA-R being only one aspect of a complex "activation reaction". To test this hypothesis we have comparatively analysed adherent versus detached keratinocyte sheets for selected indicators of keratinocyte activation by immunohistochemistry. Furthermore we have identified genes via subtraction cloning which are up-regulated upon dispase-induced detachment. The analyses provided evidence for an increased transcriptional and translational activity in detached keratinocytes, as indicated by over-expression of several ribosomal components (L3 and S10 ribosomal protein) and transcription factors (initiation factor 4A, elongation factor 1alpha). Increased proliferative activity was indicated by increased expression of the proliferation markers Ki67, keratin 6 and keratin 17. Finally, several markers of keratinocyte activation such as the integrin chain alpha(v), psoriasin, glutathion-S-transferase and heparin-binding epidermal growth factor-like growth factor were up-regulated. Furthermore mevalonate kinase, a molecule as yet unknown to be expressed in keratinocytes, was identified. The findings provide evidence that dispase-mediated detachment in cultured keratinocytes induces a reaction, which comprises the up-regulation of a complex array of proliferation- and migration-related molecules. The pattern of which resembles the activation reaction observed in the re-epithelializing keratinocytes in vivo.

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PURPOSE: The purpose of this study was to examine the effect of creatine supplementation in conjunction with resistance training on physiological adaptations including muscle fiber hypertrophy and muscle creatine accumulation. METHODS: Nineteen healthy resistance-trained men were matched and then randomly assigned in a double-blind fashion to either a creatine (N = 10) or placebo (N = 9) group. Periodized heavy resistance training was performed for 12 wk. Creatine or placebo capsules were consumed (25 g x d(-1)) for 1 wk followed by a maintenance dose (5 g x d(-1)) for the remainder of the training. RESULTS: After 12 wk, significant (P < or = 0.05) increases in body mass and fat-free mass were greater in creatine (6.3% and 6.3%, respectively) than placebo (3.6% and 3.1%, respectively) subjects. After 12 wk, increases in bench press and squat were greater in creatine (24% and 32%, respectively) than placebo (16% and 24%, respectively) subjects. Compared with placebo subjects, creatine subjects demonstrated significantly greater increases in Type I (35% vs 11%), IIA (36% vs 15%), and IIAB (35% vs 6%) muscle fiber cross-sectional areas. Muscle total creatine concentrations were unchanged in placebo subjects. Muscle creatine was significantly elevated after 1 wk in creatine subjects (22%), and values remained significantly greater than placebo subjects after 12 wk. Average volume lifted in the bench press during training was significantly greater in creatine subjects during weeks 5-8. No negative side effects to the supplementation were reported. CONCLUSION: Creatine supplementation enhanced fat-free mass, physical performance, and muscle morphology in response to heavy resistance training, presumably mediated via higher quality training sessions.

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The Scheimpflug principle was recommended as allowing distortion-free imaging; however, a detailed analysis reveals geometrical errors as well as distortions arising from absorption of light along the optical pathway. Correction formulas and factors will be presented and applied to the biometry of the eye.

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The aqueous vanadyl ion ([VO(H(2)O)(5)](2+)) has been investigated by X-band EPR, 94 GHz W-band EPR, and ESE-ENDOR. These experiments reveal information about the hyperfine (|A(xx)| = 208.5 MHz, |A(yy)| = 208.5 MHz, |A(zz)| = 547.0 MHz), and nuclear quadrupole coupling (|e(2)qQ| = 5.6 MHz) of the (51)V nucleus. The measured nuclear quadrupole coupling parameters are compared to values determined by density functional theory calculations (|e(2)qQ| = 5.2 MHz). These theoretical calculations illustrate that axial ligands and molecular distortions can alter the magnitude of the nuclear quadrupole interaction.

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In General Practice, a global measure for quality control has not yet been established. Procedures in this field of health care are usually not evidence based but rely on personal experience. In 1976, the "Diagnostic Protocols" (DP) had been introduced by Robert N. Braun to cover the most frequent and most important uncharacteristic complaints presented to the General Practitioner by the patient. In this study, the authors are showing how often the usage of DP may be useful in the management of cases in General Practice. Additionally, reasons are demonstrated that may lead the Family Physician not to apply DP in certain cases. In 2,084 new cases presented to a General Practitioner within one year (1-12/1994), 19 of 82 existing protocols were used. In every sixth new case (16%), the patient's history and physical examination were analyzed with the help of Diagnostic Protocols. However, their usage would have been beneficial in one of four cases (24.6%). Reasons for declining DP included "No need for further diagnostic investigation" and "Other diagnostic strategy chosen". Shortness of time only played a minor role.

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BACKGROUND: After a cataract surgery procedure with vitreous loss a vitreous strand remained in the wound. An unusual visual impairment was observed. PATIENT: A shift in refraction depending on the pupillary diameter was observed. In miosis the refraction was estimated to +1.0 sph, in mydriasis -1.0 sph/ -0.5 cyl, respectively. METHOD: We presumed that the vitreous strand between the iris and the intraocular lens caused an axial displacement of the IOL during the change from miosis to mydriasis and v.v. Therefore the vitreous strand was surgically eliminated. After surgery the refractive changes by pupillary actions were overcome. In a computer simulation (ray tracing), the amount of axial displacement of the IOL was estimated to 1.5 mm. CONCLUSION: This paper reminds of considering other reasons for loss of VA than CME, e.g. axial displacement of IOL. An adequate method of examination is the measurement of refraction in miosis and mydriasis.

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