The intraspecies diversity of C. albicans triggers qualitatively and temporally distinct host responses that determine the balance between commensalism and pathogenicity.

The host immune status is critical for preventing opportunistic infections with Candida albicans. Whether the natural fungal diversity that exists between C. albicans isolates also influences disease development remains unclear. Here, we used an experimental model of oral infection to probe the host response to diverse C. albicans isolates in vivo and found dramatic differences in their ability to persist in the oral mucosa, which inversely correlated with the degree and kinetics of immune activation in the host. Strikingly, the requirement of interleukin (IL)-17 signaling for fungal control was conserved between isolates, including isolates with delayed induction of IL-17. This underscores the relevance of IL-17 immunity in mucosal defense against C. albicans. In contrast, the accumulation of neutrophils and induction of inflammation in the infected tissue was strictly strain dependent. The dichotomy of the inflammatory neutrophil response was linked to the capacity of fungal strains to cause cellular damage and release of alarmins from the epithelium. The epithelium thus translates differences in the fungus into qualitatively distinct host responses. Altogether, this study provides a comprehensive understanding of the antifungal response in the oral mucosa and demonstrates the relevance of evaluating intraspecies differences for the outcome of fungal-host interactions in vivo.

Single-electron pulses for ultrafast diffraction.

Visualization of atomic-scale structural motion by ultrafast electron diffraction and microscopy requires electron packets of shortest duration and highest coherence. We report on the generation and application of single-electron pulses for this purpose. Photoelectric emission from metal surfaces is studied with tunable ultraviolet pulses in the femtosecond regime. The bandwidth, efficiency, coherence, and electron pulse duration are investigated in dependence on excitation wavelength, intensity, and laser bandwidth. At photon energies close to the cathode's work function, the electron pulse duration shortens significantly and approaches a threshold that is determined by interplay of the optical pulse width and the acceleration field. An optimized choice of laser wavelength and bandwidth results in sub-100-fs electron pulses. We demonstrate single-electron diffraction from polycrystalline diamond films and reveal the favorable influences of matched photon energies on the coherence volume of single-electron wave packets. We discuss the consequences of our findings for the physics of the photoelectric effect and for applications of single-electron pulses in ultrafast 4D imaging of structural dynamics.

[Importance of home care personally to individuals with advanced cancer and their families]. / Persönliche Bedeutung der Home Care für Kranke mit fortgeschrittenen Malignomen und deren Familien.

OBJECTIVE: The objective of the study is to evaluate the importance of home care for patients with advanced tumor diseases and for their families. METHODS: The analysis was based on structured interviews with relatives of patients with terminal tumor diseases. They had participated in the home care of 50 consecutively treated patients 2 years previously. The value of home care was evaluated on the basis of the personal experience of those concerned. RESULTS: The answers were largely consistent. The holistic concept of palliative therapy could be implemented by a specialized home care team at a high quality level. Under the favorable conditions of the familiar surroundings, an atmosphere of trust developed as a result of the cooperation with the family members, people close to the patients and with family doctors. It contributed to a relatively high quality of life and to alleviate the emotional stress. Most of those involved were able to accept the hand of fate. On this basis, the terminal phase could be satisfactorily arranged and preparations made for a good quality of death. During the home care, appreciation of the value of the family increased. The intensified family relations were mostly sustained after the patient's death. The results document the great personal importance of home care for patients, their caretakers and families. CONCLUSION: The positive experience and the awareness of having contributed substantially to coping with the life crisis made it easier for the bereaved to grieve and to rearrange their life.

In vitro and in vivo evaluation of water penetration through skin protectant barriers.

BACKGROUND/AIMS: To evaluate moisture penetration through thin films of skin protectants both in vivo and in vitro. METHODS: Fourier transform infrared (FTIR) spectroscopy was used in the reflectance mode. The in vivo studies involved moisture penetration through skin in the absence and presence of thin skin protectant films on the forearm. Moisture penetration through the stratum corneum was monitored by peeling layers of stratum corneum with Scotch(tm) tape. The in vitro studies involved the use of a 1 mm thick film of the skin protectant products on the window of the attenuated total reflectance (ATR) cell. The moisture penetration in both cases was determined by monitoring the water band at 3300 cm(-1) . The two products evaluated were petrolatum and iLEX®. RESULTS/CONCLUSIONS: Both the in vivo and in vitro results suggest that FTIR reflectance spectroscopy can be used to determine moisture penetration through skin protectant barrier films.

Suboptimal treatment results with the Therasonics lithotriptor.

From July 1988 to August 1991, 174 stone treatments were attempted on 112 stones in 86 patients using a Therasonics lithotriptor. Mean stone diameter was 13 mm. (range 4 to 60). The success rate (defined as no debris or fragments less than 4 mm. in an asymptomatic patient) was 49% and the retreatment rate was 63%. Subjects reported moderate to severe pain during 70 treatment sessions (42%) despite sedation with parenteral narcotics (50 to 100 mg. meperidine and 50 mg. hydroxyzine intramuscularly). One patient had perirenal bleeding requiring a 7-unit blood transfusion. Of the treatments 24 (13%) were aborted, 10 due to pain and 13 because of inability of the operator to position the patient or localize the stone. These results appear to be inferior to those reported with alternative lithotriptors. Modifications that have been made in the Therasonics system may improve stone localization and treatment results.

Acute effects of simulated microgravity on heart rate variability.

Microgravity is known to stress the heart and blood vessels and to perturb the normal neural regulation of the cardiovascular system. In an effort to gain greater insight into the adjustments of neural control of the cardiovascular system in space, we have used a model of simulated microgravity, the -6 degrees head-down tilt body position (HDT). As a common method for the description of the functional state of the cardiovascular system the power spectral analysis of the heart rate can be used. The following working hypotheses were postulated: 1. HDT causes an acute activation of the parasympathetic nerve traffic to the heart, which is detectable by a reduction in heart rate and by the spectral power distribution of the heart rate variability. 2. HDT induces changes in the autonomic nervous response to upright posture which can be detected after a 45-minute period of head-down tilt.

Proliferation and collagen biosynthesis of osteoblasts and chondrocytes in short rib syndrome type beemer.

We report on a case of lethal short-limbed skeletal dysplasia with extremely short ribs, median cleft upper lip and palate, malrotation of intestine, lung hypoplasia with bilateral segmentation defect, atrial septum defect, union of distal urethra and vagina, and complex brain malformations. Based on radiological criteria and the pattern of associated abnormalities a short rib syndrome without polydactyly (Type Beemer) was diagnosed. Morphologically, the growth plate showed a reduced proliferation zone and an enlarged zone of hypertrophic cartilage. In addition, islands of persistent hypertrophic cartilage were present even in the metaphysis. In monolayer cell cultures supplemented with 10% fetal calf serum proliferation was normal in articular chondrocytes, reduced in costal chondrocytes, and elevated in osteoblasts from the patient. Clonal growth of costal and articular chondrocytes in methylcellulose could be stimulated normally by insulin-like growth factor-I (IGF-I), IGF-II, and human growth hormone (hGH). However, the response to transforming growth factor beta 1 (TGF-beta 1) was markedly elevated in articular chondrocytes of the patient compared to those of 3 fetal controls. Quantitative collagen synthesis in both osteoblasts and chondrocytes from the patient did not differ significantly from that of controls. Osteoblasts synthesized predominantly collagen I and minor amounts of collagen III, chondrocytes synthesized primarily collagen II. All collagen chains including CNBr-peptides of collagen II showed normal migration in PAA gel electrophoresis.

Relation between height and the maximum conduction velocity of the ulnar motor nerve in human subjects.

The maximum motor nerve conduction velocity of the right and left ulnar motor nerve was measured in more than 650 healthy medical students of both sexes. There was no side difference in the maximum conduction velocity. The shorter person has a statistically significant higher conduction velocity than the taller person. Comparison of students of both sexes showed a slightly higher conduction velocity in females. However, with regard to its relation to height, the conduction velocity was higher in males.

Intact inhibition of the stretch reflex during general tetanus.

Tetanus toxin at lethal doses (2-10 x 10(3) mouse minimal lethal doses per kg body weight, mMLD/kg) was injected i.v. into 10 cats under pentobarbital anaesthesia. After the appearance of the first sign of generalized tetanus the animal was anaesthetized by a mixture of urethane and chloralose. Experiments were performed several hr thereafter when the toxin action was anticipated to be optimal. The stretch reflexes were elicited manually, by the contraction of the antagonistic muscles or by a stretch device. In toxin treated animals the spontaneous electromyographic activity was inhibited by strong stretching of the tested muscle or by that of the antagonistic muscle. The stretch reflex of the extensor muscle elicited by a contraction of the flexor muscle was inhibited by electrical stimulation of the flexor afferent fibres. The stretch reflex elicited by a stretch device as well as the electrically elicited monosynaptic reflex were inhibited by conditioning stimulation of the antagonistic nerve. The inhibition curves were almost the same as those of healthy animals. It is concluded that the spinal inhibitions, such as antagonistic group Ia, autogenic group Ib, groups II and III and the presynaptic inhibitions, were kept intact in severe general tetanus.

Establishment of TEST-yolk buffer enhanced sperm penetration assay limits for fertile males.

TEST-yolk buffer has been shown to enhance sperm penetration of zona-free hamster eggs. Review of sperm penetration assay (SPA) data from a fertile population was undertaken to determine a normal range for SPA with TEST-yolk buffer enhancement. Thirty-eight intrauterine insemination patients and 4 artificial insemination donors who had successfully initiated a pregnancy within 18 months of SPA analysis were examined. All 42 enhanced SPAs demonstrated penetration of greater than 10%, and 37 of these (88%) yielded SPA values of greater than or equal to 20%. Thirty-three percent (14/42) of these individuals achieved 0% penetration in the SPA without TEST-yolk buffer. The SPA performed with the TEST-yolk modification has fewer false negatives than the assay done with the original methodology.

Ioversol for intravenous urography: a comparison study.

A new nonionic, low-osmolar iodinated contrast media, ioversol, was compared with another low-osmolar, nonionic contrast media, iohexol, in 80 patients undergoing intravenous urography. There were 40 patients in each contrast group. Patients were assessed for changes in vital signs, patient tolerance (heat and pain), and other adverse effects. Double-blind evaluation was also performed for comparison of the urogram image quality. There were no severe, life-threatening reactions for either contrast group. Ten patients (25%) receiving ioversol and seven (17.5%) receiving iohexol perceived body heat related to the injection of contrast material. Two patients (5%) in each group experienced mild nausea. Two patients (5%) of each group experienced noted unpleasant taste, and two patients (5%) of the iohexol group complained of headache. Vital signs remained stable without significant change in both groups, and image quality was considered equivalent. The results indicate that the two contrast agents are equivalent in image quality, safety, and incidence of adverse effects.

Presynaptic inhibition of the monosynaptic reflex during local tetanus in the cat.

Tetanus toxin at doses of 2-2000 mouse MLD/kg was injected into the gastrocnemius muscle of the left hind limb of the cat. Acute experiments were performed at various times thereafter, when the intoxicated hind leg was strongly extended. Presynaptic inhibition of the monosynaptic reflex (MSR) of gastrocnemius motoneurones was tested by applying conditioning single electric stimuli to the antagonistic deep peroneal nerve. In most intoxicated animals the delayed inhibition of the MSR could still be observed at time intervals typical for presynaptic inhibition. However, the amplitude of the MSR often showed a strong toxin-induced facilitation at about 30 msec after the conditioning stimulus which could mask the presynaptic inhibition and sometimes made it difficult to observe it at all. After spinal transection at the Th1 level the inhibition could be better observed in such cases. Further evidence for the resistance of the presynaptic inhibitory system against the tetanus toxin in the given dose range was given by recordings of distinct dorsal root potentials which were abolished, together with the MSR inhibition by i.v. injection of picrotoxin. It is concluded that the mechanism of presynaptic inhibition remains intact or is even lengthened during local tetanus after i.m. injection of moderate, clinically relevant, toxin doses.

Blocking effects of tetanus toxin and its fragment [A-B] on the excitatory and inhibitory synapses of the spinal motoneurone of the cat.

A highly purified fragment [A-B] preparation (5.5 micrograms of protein in 5 or 10 microliters which is far less than the minimal lethal dose), free from contamination with the whole toxin, was injected intraspinally into the neighbouring area of the gastrocnemius motoneurone pool (eight cats). Tetanus toxin (27 micrograms protein, about 100 LD50) in 5 or 10 microliters (four cats) and 10 microliters of Ringer's solution (four cats) were injected in the same way. Fragment [A-B] depressed both the monosynaptic reflex (MSR) of the gastrocnemius motoneurone pool and its inhibition by conditioning stimulus on the antagonistic peroneal nerve almost simultaneously in the individual cats, in contrast to the whole toxin which blocked first the inhibition of the MSR and later the MSR itself. The effects of fragment [A-B] appeared late, at about the time when the whole toxin blocked the MSR. The cats injected with fragment [A-B] did not die by intoxication. Fragment [A-B] at high doses (up to 120 micrograms) injected intramuscularly into the rat had no effect on neuromuscular transmission. The results clearly showed a blocking action of fragment [A-B] on inhibitory and excitatory synapses of the spinal motoneurones.

MMPI response-set characteristics among adolescents.

This study examined the Minnesota Multiphasic Personality Inventory (MPPI) profile characteristics for five different response sets in adolescent populations employing adolescent MMPI norms. In general, findings for "all-true" and "all-false" adolescent profiles were highly similar in shape and elevation to those reported in the adult literature (Graham, 1977; Lachar, 1974), whereas random profiles on adolescent norms differed substantially from adult-norm random profiles in shape but not elevation. The characteristics of "fake good" or "fake bad" response sets were investigated by the use of adolescent subjects in two settings. Ninety-four public high-school students were administered the MMPI with standard and "fake bad" instructions, and 24 adolescents in inpatient psychiatric treatment were administered the MMPI under standard and "fake good" instructions. The MMPI profiles generated by special instructional sets were analyzed in relation to the subject's age, sex, race, and actual MMPI profile features. Findings indicated that although sex and race effects were evident in normal adolescents' attempts to simulate psychopathology on the MMPI, teenagers generally produce profiles containing grossly exaggerated symptom patterns that are relatively easy to detect as invalid. In contrast, it was found that a substantial number of psychiatrically disturbed adolescents may effectively simulate normal profiles and that effectiveness in these attempts was related to greater age and lower actual MMPI T-score values on the Hs and Hy scales.

Treatment of carcinoma of the penis: the case for primary lymphadenectomy.

There were 65 patients with squamous cell carcinoma of the penis followed for a minimum of 5 years. Patients with stage I disease uniformly survived with local treatment only. Of the patients with stages II and III carcinoma of the penis 88 and 66 per cent, respectively, were free of disease if lymphadenectomy was performed shortly following treatment of the primary lesion, compared to only 38 and 0 per cent, respectively, if the primary lesion was treated locally and no lymphadenectomy was performed. These data support the concept that lymphadenectomy should be an integral part of the primary treatment in patients with stages II and III penile cancer.

Renal vascular injuries.

Fifteen patients with injuries to the renal arteries and/or veins have been treated in the past ten years. Nine injuries were the result of gunshot wounds, and six were from blunt trauma. Twelve patients presented to the emergency department in shock; two of these did not have a palpable blood pressure. Time from admission to time of operation averaged 6.4 hr for patients with blunt trauma and 1.25 hr for patients with penetrating trauma. Seven patients had ten associated abdominal vascular injuries, and two patients had injuries to both the right renal artery and left renal vein. Associated nonvascular abdominal injuries were found in all 15 patients. Efforts were made to repair renal vascular injuries with suture or grafting of the injured vessel in eight cases (53%). These efforts were successful in four patients, but in four the repair failed and a nephrectomy could not be avoided. Two patients died in the operating room or immediately postop in spite of successful repair of their renovascular injury. One injured left renal vein was ligated and nephrectomy was not necessary. In five patients, ligation of the injured renal artery and nephrectomy were necessary. There were five deaths (33%). Three of the deaths occurred in the operating room and two were postoperative deaths. Only one of the patients who died had a renal vessel injury without other major vessels involved. He did, however, have serious liver and kidney injuries. Multiple associated vascular, nonvascular, and head injuries were present in all four of the other deaths. We have continued to take an aggressive approach to exploration, isolation of the injury, and repair of the vessel whenever possible if a renal vessel injury is suspected.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative assessment of rabbit alveolar macrophage function by chemiluminescence.

Rabbit alveolar macrophages (RAM) were cultured for 24 hr with concentrations ranging from 3 to 12 micrograms/ml of vanadium oxide (V2O5), a known cytotoxic agent, or with high-molecular-weight organic by-products from coal gasification processes. After culture the cells were harvested and tested for functional capacity using three types of indicators: (1) luminol-amplified chemiluminescence (CL), which quantitatively detects photon emission due to respiratory burst activity measured in a newly designed instrument with standardized reagents; (2) the reduction of nitro blue tetrazolium-saturated polyacrylamide beads, a semiquantitative measure of respiratory burst activity; and (3) phagocytic efficiency, defined as percentage of cells incorporating immunoglobulin-coated polyacrylamide beads. Chemiluminescence declined linearly with increasing concentrations of V2O5 over the dose range tested. Dye reduction and phagocytic efficiency similarly decreased with increasing V2O5 concentration, but were less sensitive indicators of functional impairment than CL as measured by the amount required to reduce the response to 50% of untreated cells. The effect of coal gasification condensates on RAM function varied, but in general these tests also indicated that the CL response was the most sensitive indicator.

Effect of propranolol on lecithin:cholesterol acyl transferase activity in vitro.

Recently propranolol was found to inhibit human lecithin: cholesterol acyl transferase (LCAT) activity both after oral treatment and after addition to plasma in vitro. Now the dose-response relationship of the propranolol effect on LCAT activity was evaluated in vitro. Concentrations required to produce half-maximal effects in 7 men ranged from 32.4 to 121.4 nmol/l which corresponds to the therapeutical concentration range of the drug. Complete inhibition could not be achieved. The maximal effect (propranolol-sensitive LCAT activity) varied between subjects depending on the preexiting lecithin: cholesterol acyl transfer rate in plasma. Propranolol mediated inhibition of LCAT activity could be abolished when heat-inactivated plasma instead of native plasma was used as LCAT substrate. It is concluded that the interindividual variability of propranolol-sensitive LCAT activity may reflect differences in the thermoinstable lipoprotein structure.

Advantages of nonionic contrast agents in adult urography.

Nonionic radiographic contrast agents have a reported advantage of decreased contrast osmolality. Before clinical significance can be attributed to this lower osmolality, an observed difference must be documented. In a randomized double-blind study with 55 patients, Iohexol, a new nonionic contrast agent, is compared with Renografin 60 for use in adult urography. Hemodynamic parameters, serum and urine chemistries, including osmolality, were recorded before and after contrast injection. Radiographic quality and adverse reactions were recorded. This study focused on the change in urine osmolality (delta Osm) from pre- and post-injection urine specimens. The group receiving nonionic contrast agents had an average delta Osm of 65 mOsm/L while those receiving the ionic agent had an average delta Osm of 120 mOsm/L. This significant difference in urine osmolality is discussed with respect to the observed advantage in radiographic quality and the lower incidence of adverse reactions noted in the group receiving nonionic contrast material.