Treatment outcome of atypical EGFR mutations in the German National Network Genomic Medicine Lung Cancer (nNGM).

BACKGROUND: Atypical EGFR mutations occur in 10%-30% of non-small-cell lung cancer (NSCLC) patients with EGFR mutations and their sensitivity to classical epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) is highly heterogeneous. Patients harboring one group of uncommon, recurrent EGFR mutations (G719X, S768I, L861Q) respond to EGFR-TKI. Exon 20 insertions are mostly insensitive to EGFR-TKI but display sensitivity to exon 20 inhibitors. Clinical outcome data of patients with very rare point and compound mutations upon systemic treatments are still sparse to date. PATIENTS AND METHODS: In this retrospective, multicenter study of the national Network Genomic Medicine (nNGM) in Germany, 856 NSCLC cases with atypical EGFR mutations including co-occurring mutations were reported from 12 centers. Clinical follow-up data after treatment with different EGFR-TKIs, chemotherapy and immune checkpoint inhibitors were available from 260 patients. Response to treatment was analyzed in three major groups: (i) uncommon mutations (G719X, S7681, L861Q and combinations), (ii) exon 20 insertions and (iii) very rare EGFR mutations (very rare single point mutations, compound mutations, exon 18 deletions, exon 19 insertions). RESULTS: Our study comprises the largest thus far reported real-world cohort of very rare EGFR single point and compound mutations treated with different systemic treatments. We validated higher efficacy of EGFR-TKI in comparison to chemotherapy in group 1 (uncommon), while most exon 20 insertions (group 2) were not EGFR-TKI responsive. In addition, we found TKI sensitivity of very rare point mutations (group 3) and of complex EGFR mutations containing exon 19 deletions or L858R mutations independent of the combination partner. Notably, treatment responses in group 3 (very rare) were highly heterogeneous. Co-occurring TP53 mutations exerted a non-significant trend for a detrimental effect on outcome in EGFR-TKI-treated patients in groups 2 and 3 but not in group 1. CONCLUSIONS: Based on our findings, we propose a novel nNGM classification of atypical EGFR mutations.

Development and validation of technologies suitable for the decontamination and re-use of contaminated N95 filtering facepiece respirators in response to the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has brought significant challenges to society globally, particularly in the area of healthcare provision. A pressing need existed in protecting those tasked with delivering healthcare solutions during the COVID-19 crisis by providing solutions for preserving adequate supplies of effective personal protective equipment (PPE). AIM: To evaluate and validate available methods for the decontamination of N95 filtering facepiece respirators (FFRs) while maintaining functionality during re-use. METHODS: Multiple low-temperature steam and vaporized hydrogen peroxide (VHP) technologies were assessed for inactivation of Mycobacterium spp. and feline calicivirus (employed as representatives of the contamination challenge). FINDINGS: Virus (≥3log10) and Mycobacterium spp. (≥6log10) inactivation was achieved on various types of N95 FFRs using an array of heat (65-71oC), humidity (>50% relative humidity) and VHP without affecting the performance of the PPE. CONCLUSION: The methods have been validated and were authorized by the US Food and Drug Administration under a temporary emergency use authorization. Based on the findings, opportunities exist for development and deployment of decontamination methods made from simple, general purpose materials and equipment should a future need arise.

The Olfactory Cleft Endoscopy Scale: a multi-institutional validation study in chronic rhinosinusitis.

BACKGROUND: Olfactory dysfunction (OD) associated with chronic rhinosinusitis (CRS) remains quite challenging. Instruments to precisely assess olfactory cleft anatomy and their association with olfaction are needed. METHODS: The olfactory cleft endoscopy scale (OCES) was used to assess the olfactory cleft in healthy control subjects and a cohort of patients with CRS. Psychophysical and psychosocial olfactory function were assessed and correlations with OCES scores were measured. RESULTS: Control subjects and subjects with CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) were enrol- led. OCES correlated with both psychophysical and psychosocial olfaction, as measured by threshold, discrimination and identi- fication (TDI) scores and Questionnaire on Olfactory Disorders (QOD-NS) scores for all case and control subjects combined. OCES improved in both CRS groups postoperatively with the highest correlation seen in postoperative olfaction in CRSwNP patients. CRS patients who achieve near perfect OCES and sinus endoscopy scores after surgery have olfactory metrics that are indistin- guishable from controls regardless of polyp status. CONCLUSIONS: The OCES is a valid olfactory-specific measure that demonstrates strong validity and provides complimentary infor- mation to traditional sinus endoscopy to aid in our understanding of OD associated with CRS.

[Epidemiological Study of the Effects of Gender, Age, Mobility and Time of Injury on Proximal Femoral Fractures]. / Epidemiologická studie vlivu pohlaví, veku, mobility a doby úrazu na zlomeniny proximálního femuru.

PURPOSE OF STUDY Based on the selected criteria the study presents the evaluation of data of patients who underwent a surgery for proximal femoral fracture at the Department of Orthopaedic Trauma of the 1 st Faculty of Medicine and Military University Hospital Prague in the period 2013-2016. The paper aimed to determine whether there are any differences in proximal femoral fractures depending on the selected criteria. MATERIAL AND METHODS The study comprised 805 patients (562 women and 243 men) older than 21 years with proximal femoral fractures who were treated between January 1, 2013 and December 31, 2016. In the study, the patient s data on gender, age, a type of fracture (according to the AO classification), a level of mobility, time of injury and month of injury were analysed. The data was evaluated using the methods of descriptive statistics, one-way analysis of variance, two-way analysis by ANOVA and by following select POST-HOC test (Fisher LSD test) were utilized, 95% confidence interval was selected . RESULTS In the group of treated patients, the men were outnumbered by women (70% vs. 30%). In women the fractures occurred at a significantly (p < 0.001) older age (82 years) compared to men (77 years). Until the 8 th decade the fractures in men dominated, while from the 9th decade the fractures were more frequent in women. A sharp increase in the number of fractures in women was reported exactly in the 9th decade (56% of the total number of fractures in women). The group of women showed a significant difference (p = 0.027) between the age of femoral neck fractures and the age of trochanteric femoral fractures (80 years vs. 84 years). In both genders intracapsular and pertrochanteric fractures prevailed. In women and men with a limited mobility, fractures were sustained at the highest mean age (85 years in women, 84 years in men) compared to the other levels of mobility. In mobile patients, a significant difference (p < 0.001) was found between the age of women and men at which the fracture was sustained (79 years vs. 71 years). The largest significant difference (p < 0.001) in the age of fracture is seen in night time (84 years in women, 71 years in men). The highest number of injuries was suffered in the months of October to January, whereas the lowest number was reported in the period from June to July. DISCUSSION The epidemiological studies underline a notably higher incidence of proximal femoral fractures in women than in men, which was also confirmed by our study. The mean age of women with proximal femoral fracture was significantly higher compared to men. Similar conclusions have been drawn also by other studies. The incidence of fractures in dependence on the age group was the highest in women and men in their 9th decade, which compared to the previous studies was at a later age. This finding can be justified by aging of the Czech population, with the growing number of persons in the 9 th decade age group between 2012 and 2017 by 40,000. Nonetheless, men prevailed in fractures until the 9 th decade, while from the 9 th decade there is a marked growth in the number of these fractures sustained by women. This corresponds with the findings of other authors. As to the individual types of fractures (neck, trochanteric fracture) no difference was revealed in the percentage of women and men. In both genders intracapsular and petrochanteric fractures prevailed. Neither the level of pre-fracture mobility, nor the time of injury have been sufficiently monitored and evaluated with regard to the age of patients, therefore there is no adequate data to compare our results with. The lowest mean age at the time of injury was achieved by fully mobile men (71 years), which can be attributable to their sports and social activities performed at this age. The highest number of proximal femoral fractures was reported in the period from October to January, whereas their lowest number was reported in the period from June to July, which corresponds with the majority of other conducted studies in this area of research. CONCLUSIONS A considerably higher incidence of proximal femoral fractures in women was confirmed. The mean age of women with proximal femoral fracture was significantly higher than in men (82 vs. 77 years). Men prevailed in the number of fractures up to the 9 th decade, whereas from the 9 th decade the number of proximal femoral fractures in women significantly grew. In individual types of fractures (neck, trochanteric fractures), no difference in percentage of women and men was found. In both the genders intracapsular and pertrochanteric fractures significantly prevailed. The lowest mean age (71 years) at the time of injury was achieved by fully mobile men. The same age was identified in men also with respect to injuries sustained at night. The highest number of proximal femoral fractures was reported in the period from October to January, the lowest in the period from June to July. The knowledge of these seasonal variations can help plan the health care in the medical facility concerned. Key words: proximal femur, fracture, gender, mobility, day-time, seasonality.

[Intramedullary injection with tethered cord : Case report of a rare complication during spinal anesthesia]. / Intramedulläre Injektion bei "tethered cord" : Fallbericht einer seltenen Komplikation bei Spinalanästhesie.

Although very rare, severe neurological complications can occur when undergoing spinal anesthesia. This report describes and analyses a case of spinal injury due to an undiagnosed tethered cord (TC) during spinal anesthesia for a cesarean section of a 31-year-old woman expecting twins. As a consequence of spinal dysraphism during embryogenesis, an atypically low conus level can occur and increase the risk of injury during neuraxial anesthesia, especially in the absence of symptoms. Injuries can be caused by mechanical trauma from direct needle injury, hematoma or neurotoxicity from local anesthetics. Special attention should therefore be paid to frequent symptoms, such as a hairy nevus on the back, deformities of the feet or bladder and bowels, voiding and micturition dysfunction in order to reduce the risk of complications.

Evolutionary diversification of the auditory organ sensilla in Neoconocephalus katydids (Orthoptera: Tettigoniidae) correlates with acoustic signal diversification over phylogenetic relatedness and life history.

Neoconocephalus Tettigoniidae are a model for the evolution of acoustic signals as male calls have diversified in temporal structure during the radiation of the genus. The call divergence and phylogeny in Neoconocephalus are established, but in tettigoniids in general, accompanying evolutionary changes in hearing organs are not studied. We investigated anatomical changes of the tympanal hearing organs during the evolutionary radiation and divergence of intraspecific acoustic signals. We compared the neuroanatomy of auditory sensilla (crista acustica) from nine Neoconocephalus species for the number of auditory sensilla and the crista acustica length. These parameters were correlated with differences in temporal call features, body size, life histories and different phylogenetic positions. By this, adaptive responses to shifting frequencies of male calls and changes in their temporal patterns can be evaluated against phylogenetic constraints and allometry. All species showed well-developed auditory sensilla, on average 32-35 between species. Crista acustica length and sensillum numbers correlated with body size, but not with phylogenetic position or life history. Statistically significant correlations existed also with specific call patterns: a higher number of auditory sensilla occurred in species with continuous calls or slow pulse rates, and a longer crista acustica occurred in species with double pulses or slow pulse rates. The auditory sensilla show significant differences between species despite their recent radiation, and morphological and ecological similarities. This indicates the responses to natural and sexual selection, including divergence of temporal and spectral signal properties. Phylogenetic constraints are unlikely to limit these changes of the auditory systems.

Clinical Impact of Ventilation Duration in Patients with Stroke Undergoing Interventional Treatment under General Anesthesia: The Shorter the Better?

BACKGROUND AND PURPOSE: Whether general anesthesia for neurothrombectomy in patients with ischemic stroke has a negative impact on clinical outcome is currently under discussion. We investigated the impact of early extubation and ventilation duration in a cohort that underwent thrombectomy under general anesthesia. MATERIALS AND METHODS: We analyzed 103 consecutive patients from a prospective stroke registry. They met the following criteria: CTA-proved large-vessel occlusion in the anterior circulation, ASPECTS above 6 on presenting cranial CT, revascularization by thrombectomy with the patient under general anesthesia within 6 hours after onset of symptoms, and available functional outcome (mRS) 90 days after onset. RESULTS: The mean ventilation time was 128.07 ± 265.51 hours (median, 18.5 hours; range, 1-1244.7 hours). Prolonged ventilation was associated with pneumonia during hospitalization and unfavorable functional outcome (mRS ≥3) and death at follow-up (Mann-Whitney U test; P ≤ .001). According to receiver operating characteristic analysis, a cutoff after 24 hours predicted unfavorable functional outcome with a sensitivity and specificity of 60% and 78%, respectively. Our results imply that delayed extubation was not associated with a less favorable clinical outcome compared with immediate extubation after the procedure. CONCLUSIONS: Short ventilation times are associated with a lower pneumonia rate and more favorable clinical outcome. Cautious interpretation of our data implies that whether patients are extubated immediately after the procedure is irrelevant for clinical outcome as long as ventilation does not exceed 24 hours.

Interleukin-1beta stimulates growth hormone-releasing hormone receptor mRNA expression in the rat hypothalamus in vitro and in vivo.

Changes in growth hormone-releasing hormone (GHRH), GHRH-receptor (R), somatostatin and interleukin (IL)-1beta mRNA levels were determined in fetal rat hypothalamic cultures after administration of IL-1beta (1, 10, 100 ng/ml, 2 h incubation), and in adult rat hypothalamus 5 h after intracerebroventricular injection of IL-1beta (2.5 and 25 ng). IL-1beta stimulated GHRH-R mRNA expression both in vitro (10 and 100 ng/ml) and in vivo (2.5 and 25 ng). Somatostatin mRNA was significantly stimulated and GHRH mRNA slightly reduced in vitro, while these mRNA species were not altered in vivo in response to IL-1beta. IL-1beta stimulated its own expression both in vitro (10 and 100 ng/ml) and in vivo (25 ng). IL-1beta-induced mRNA responses occurred 2 h after treatment in vitro (incubation times, 30 min to 6 h). IL-1beta also elicited slight GHRH releases in vitro. Up-regulation of hypothalamic GHRH-R by IL-1beta may explain previous findings suggesting that IL-1beta stimulates GHRH activity.

[Value of endoanal sonography in the assessment of faecal incontinence]. / Wertigkeit der Endoanalsonographie in der Abklärung bei fäkaler Inkontinenz.

PURPOSE: The aim of this study was to assess the value of endoanal ultrasound (EUS) in comparison to anal manometry and operative findings in patients suffering from faecal incontinence. Patient history, localisation of sphincter defects and therapeutic modalities were analysed. METHODS: Over a 3-years period, 92 patients with faecal incontinence were investigated by endoanal ultrasound. Results were compared with anal manometry in 81 cases. RESULTS: At EUS, 27 patients (29 %) showed no sphincter defect, 18 (20 %) had an isolated internal sphincter defect, 13 (14 %) an isolated defect of the external sphincter and 34 (37 %) presented with a combined internal/external sphincter defect. Manometry correlated in 30 % with endoanal ultrasound. Compared with surgery, endoanal ultrasound was correct in 100 % and manometry in only 54 %. An obstetric trauma was most frequently related to faecal incontinence. CONCLUSION: Endoanal ultrasound is a very sensitive method for localizing anal sphincter defects and is mandatory in the assessment of patients with faecal incontinence.

Influence of photoperiod on N-acetyltransferase activity and melatonin in the fiddler crab Uca pugilator.

Melatonin and N-acetyltransferase (NAT) activity were measured in the eyestalks of fiddler crabs acclimated to various photoperiods: constant light, a L:D 12:12 h photoperiod, or constant dark. Following acclimation, eyestalks were collected every 3 h over a 24-h period; they were assayed for melatonin with a radioimmunoassay and for NAT activity with a radioenzymatic assay. In constant light, melatonin levels increased at 1300 h, from 142 to 431 pg x mg(-1) eyestalk; NAT activity increased concurrently, from 97 to 203 pmol x h(-1) x mg(-1) eyestalk, and both remained elevated until 0400 h. In the L:D 12:12 h photoperiod, melatonin levels increased at 1300 h from 28 to 230 pg x mg(-1) eyestalk, and though NAT activity increased significantly, from 80 to 122 pmol x h(-1) x mg(-1) eyestalk, an even greater increase occurred at 0400 h, when melatonin levels were low. In constant dark, melatonin levels increased at 1600 h, from 22 to 196 pg x mg(-1) eyestalk, with a concurrent increase in NAT activity from 93 to 140 pmol x mg(-1) x h(-1) eyestalk. However, the second peak in melatonin (111 pg x mg(-1)), occurring at 0400 h, was out of phase with the second peak of NAT activity (113 pmol x mg(-1) x h(-1) eyestalk) which occurred at 0700 h. NAT may be a rate-limiting step in melatonin synthesis in fiddler crabs under some conditions (constant light and the 1300 h peak in constant dark); however, NAT activity correlates poorly with melatonin levels in a L:D 12:12 h photoperiod and in constant dark relative to the 0400 h melatonin peak.

Oxygen isotope ratios of PO4: an inorganic indicator of enzymatic activity and P metabolism and a new biomarker in the search for life.

The distinctive relations between biological activity and isotopic effect recorded in biomarkers (e.g., carbon and sulfur isotope ratios) have allowed scientists to suggest that life originated on this planet nearly 3.8 billion years ago. The existence of life on other planets may be similarly identified by geochemical biomarkers, including the oxygen isotope ratio of phosphate (delta(18)O(p)) presented here. At low near-surface temperatures, the exchange of oxygen isotopes between phosphate and water requires enzymatic catalysis. Because enzymes are indicative of cellular activity, the demonstration of enzyme-catalyzed PO(4)-H(2)O exchange is indicative of the presence of life. Results of laboratory experiments are presented that clearly show that delta(18)O(P) values of inorganic phosphate can be used to detect enzymatic activity and microbial metabolism of phosphate. Applications of delta(18)O(p) as a biomarker are presented for two Earth environments relevant to the search for extraterrestrial life: a shallow groundwater reservoir and a marine hydrothermal vent system. With the development of in situ analytical techniques and future planned sample return strategies, delta(18)O(p) may provide an important biosignature of the presence of life in extraterrestrial systems such as that on Mars.

Phosphorylation-dependent regulation of cyclin D1 nuclear export and cyclin D1-dependent cellular transformation.

GSK-3beta-dependent phosphorylation of cyclin D1 at Thr-286 promotes the nuclear-to-cytoplasmic redistribution of cyclin D1 during S phase of the cell cycle, but how phosphorylation regulates redistribution has not been resolved. For example, phosphorylation of nuclear cyclin D1 could increase its rate of nuclear export relative to nuclear import; alternatively, phosphorylation of cytoplasmic cyclin D1 by GSK-3beta could inhibit nuclear import. Here, we report that GSK-3beta-dependent phosphorylation promotes cyclin D1 nuclear export by facilitating the association of cyclin D1 with the nuclear exportin CRM1. D1-T286A, a cyclin D1 mutant that cannot be phosphorylated by GSK-3beta, remains nuclear throughout the cell cycle, a consequence of its reduced binding to CRM1. Constitutive overexpression of the nuclear cyclin D1-T286A in murine fibroblasts results in cellular transformation and promotes tumor growth in immune compromised mice. Thus, removal of cyclin D1 from the nucleus during S phase appears essential for regulated cell division.

M-1/M-2 macrophages and the Th1/Th2 paradigm.

Evidence is provided that macrophages can make M-1 or M-2 responses. The concept of M-1/M-2 fomented from observations that macrophages from prototypical Th1 strains (C57BL/6, B10D2) are more easily activated to produce NO with either IFN-gamma or LPS than macrophages from Th2 strains (BALB/c, DBA/2). In marked contrast, LPS stimulates Th2, but not Th1, macrophages to increase arginine metabolism to ornithine. Thus, M-1/M-2 does not simply describe activated or unactivated macrophages, but cells expressing distinct metabolic programs. Because NO inhibits cell division, while ornithine can stimulate cell division (via polyamines), these results also indicate that M-1 and M-2 responses can influence inflammatory reactions in opposite ways. Macrophage TGF-beta1, which inhibits inducible NO synthase and stimulates arginase, appears to play an important role in regulating the balance between M-1 and M-2. M-1/M-2 phenotypes are independent of T or B lymphocytes because C57BL/6 and BALB/c NUDE or SCID macrophages also exhibit M-1/M-2. Indeed, M-1/M-2 proclivities are magnified in NUDE and SCID mice. Finally, C57BL/6 SCID macrophages cause CB6F1 lymphocytes to increase IFN-gamma production, while BALB/c SCID macrophages increase TGF-beta production. Together, the results indicate that M-1- or M-2-dominant macrophage responses can influence whether Th1/Th2 or other types of inflammatory responses occur.

Traumatic acetabular fracture in an intercollegiate football player: a case report.

OBJECTIVE: To present the case of a 22-year-old football player who sustained an acute posterior-wall acetabular fracture. BACKGROUND: Acetabular fractures can be a difficult injury for the athletic trainer to assess. Aside from the obvious immediate ramifications, proper assessment and care are necessary to decrease the chance of developing posttraumatic arthritis and other long-term complications. DIFFERENTIAL DIAGNOSIS: Anterior column fracture, T-shaped acetabular fracture, segmental fracture of the femoral head, femoral neck fracture, capsular tear, retroperitoneal hematoma, posterior column acetabular fracture. TREATMENT: The athlete was treated with open reduction internal fixation using 5 screws and a plate. He pursued a rehabilitation program and returned to full activity 9 months later. UNIQUENESS: Acetabular fractures are usually associated with motor vehicle accidents. However, this athlete sustained an injury mechanism that rarely occurs in athletes. CONCLUSIONS: Certified athletic trainers need to recognize the signs and symptoms associated with acetabular fractures. Initial recognition and appropriate management and treatment are essential to avoid long-term complications.

Structural analysis of angiotensin IV receptor (AT4) from selected bovine tissues.

The angiotensin IV receptor (AT4) receptor is widely distributed in both species and tissues. This broad distribution appears to be reflected in an equally diverse repertoire of physiological actions that are mediated through AT4 receptors. This breadth of location and function of AT4 receptors encourages speculation that multiple AT4 isoforms might exist. In this study, we compared the structural properties of bovine AT4 receptors from adrenals, kidney, heart, thymus, bladder, aorta, and hippocampus. These comparisons were made using polyacrylamide gel electrophoresis or HPLC analysis of AT4 receptors that had been covalently radiolabeled with the AT4-specific photoprobe 125I-benzoyl phenylalamine-angiotensin IV. Except for the hippocampal AT4 receptor, the binding subunit in all tissues had a molecular mass of approximately 165 kDa and associated with additional subunits via disulfide linkages. The hippocampal receptor was significantly smaller (150 kDa) and did not appear to possess other disulfide-linked subunits. The receptor was highly glycosylated in all tissues examined. Peptide mapping following cleavage of 125I-labeled receptor with endopeptidase C or cyanogen bromide resulted in complex cleavage patterns. Together these mapping studies demonstrated the uniqueness of the hippocampal receptor and further suggested that other AT4 isoforms may exist and be variably distributed among bovine tissues. In agreement with the peptide mapping studies, differences in the binding pattern of several AngIV analogs were observed among the various tissues.

Traumatic hyphema in an intercollegiate baseball player: a case report.

OBJECTIVE: To present the case of a collegiate baseball player struck in the right eye. BACKGROUND: While attempting a bunt, a 20-year-old collegiate baseball player was hit in the right eye when the ball was deflected off the bat. The athlete bled from the nose, and the right eye swelled shut from eyelid edema. Initial nasal hemorrhage was controlled, and the athlete was referred to the emergency room for further care due to pain in the inferior orbit. DIFFERENTIAL DIAGNOSIS: Eyelid contusion, traumatic iritis, or traumatic microhyphema to the right eye secondary to blunt trauma. TREATMENT: Immediate treatment consisted of controlling the nasal bleeding with sterile gauze pads. Because of palpable tenderness over the inferior orbit, the athlete was immediately transported to the emergency room. UNIQUENESS: Hyphema is one of the most common sport-related eye injuries: the incidence is 12.2 cases per 100,000 population, with approximately 37% resulting from sports injury. Racquet sports, baseball, and softball account for more than half of all hyphema injuries in athletics. Individuals with traumatic hyphema rarely require surgery; however, proper initial care, treatment, and referral are imperative to a good prognosis. CONCLUSIONS: Athletic trainers need to be able to recognize the signs and symptoms of hyphema and seek medical evaluation immediately in order to avoid secondary complications. With proper recognition, initial care and referral, and appropriate, well-fitted protective eyewear as needed, hyphema can have minimal complications, and the athlete may be able to compete again within 1 to 2 weeks.

HIV test counselling at a tertiary hospital.

A questionnaire was distributed to 64 of the 78 interns working at a teaching hospital in Cape Town in August 1992 to examine their attitudes and practice in respect of HIV test counselling. The questionnaire was completed by 61 interns. Thirteen per cent of those who responded counselled all patients, 49% counselled some patients and 38% counselled no patients. Thirty-four per cent stated that they felt that pre-test counselling was always necessary and 57% that post-test counselling was always necessary. The most frequently stated reasons for not counselling patients were language barriers, time constraints, feelings of incompetence on the part of the intern and the fact that the patient was too ill. It is recommended that standard counselling procedures be established in each ward and formal under- and postgraduate counselling training for medical students and interns be instituted.

The Munich Wistar Frömter rat: proteinuria and blood pressure in correlation to the number of superficial glomeruli.

Rats with a high number of superficial nephrons (MWF/Ztm) also show an elevated urinary protein excretion and a high systolic blood pressure. To investigate a possible correlation between the number of superficial glomeruli and these physiological changes, MWF/Ztm rats were crossed and backcrossed to Wistar cryptorchic (WC/Ztm) animals with no superficial nephrons in order to produce genotypes with differing numbers of superficial glomeruli. In the parental strains, the F1 hybrids and the 8 possible backcrosses, the number of superficial glomeruli, the distance of the 10 most superficial glomeruli to the renal surface, and the diameter of Bowman's capsules were determined by morphometric analysis. The excretion of total protein, in detail low molecular weight proteins, albumin, and high molecular weight proteins were measured quantitatively in 5 males of each genotype. Systolic blood pressure was determined by a tail-cuff method in conscious rats. Means of each variate of the 12 available genotypes were linearly correlated and demonstrate a close correlation between the amount of superficial nephrons and the observed physiological changes, i.e. the more superficial the glomeruli the higher the urinary protein excretion, especially albumin, and the higher the systolic blood pressure.

Study on the renal handling of sex dependent proteins in male rats studied by micropuncture techniques and by the isolated perfused rat kidney.

The separation of sex dependent urinary proteins of the rat (SDP) by micro-disc electrophoresis results in at least eight well defined protein bands with differing molecular weights. The hepatic origin of a sex dependent urinary protein, named alpha 2u-globulin, has been demonstrated before by other authors applying immunological methods. In the present study, it could been shown that SDP circulate in the plasma at a concentration of 23.8 mg/l. The origin of those protein bands which appear typically upon electrophoresis was still under dispute because they could not been demonstrated in proximal tubular fluid. The present study confirms the extrarenal source of SDP and suggests identity with alpha 2u-globulin. The attempt to track down SDP from plasma to excreted urine demonstrated that, in contrast to proximal fluid, samples from nephron parts distal to the loop of Henle contain large amounts of SDP. An isolated kidney model was used to determine the sieving coefficient and tubular reabsorption of SDP, obtained from male rat urine. We have found a correlation between the sieving coefficient and the molecular weight of SDP. The sieving coefficient ranged from 0.375 to 0.834. The tubular reabsorption which has been determined with an isolated kidney perfused with albumin and erythrocytes also showed variation with regard to molecular weight and was 61.7%, on average.