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Background: More epidemiological data about lentigo maligna melanoma (LMM) are required to define follow-up guidelines. The study focused on recurrence, progression, and overall survival of LMM managed with primary wide local excision. Methods: In a 23-year retrospective study (1994 to 2016), a cohort of patients with LMM was evaluated by collecting data about the tumor location, the Breslow depth, the presence of ulceration, and patients’ age and sex. Local recurrences, locoregional and distant metastases, and disease-free and overall survival were additionally assessed. Results: Overall, 150 cases (84 male, 66 female, mean age 71.3 ± 11.3 years) of single, localized, primary LMM with a mean follow-up of 6.6 ± 4.4 years were included. A total of 33 (22.2%) patients underwent sentinel lymph node biopsy (SLNB) during surgical excision. However, positive SLNB was detected in none of them. The multivariable Cox analysis indicated that age of diagnosis and male gender significantly influenced the overall survival, while a shorter disease-free survival could be correlated with a greater Breslow thickness. The metastatic potential turned out to be low, entailing 7 deaths in the context of the LMM. Conclusion: Male gender, age over 70 at diagnosis, and a Breslow thickness greater than 0.75 mm were associated with a statistically significant decrease in overall disease-free survival in the current study. The results of the study confirm the favorable outcome of LMM. However, diagnosed patients should undertake regular follow-ups. The intensity of follow-up in these patients can be individualized based on the probability of recurrence/metastasis and overall survival. Furthermore, the study showed that SLNB might not be a necessary staging procedure in patients with LMM.

Immune checkpoint inhibitors (ICI) have led to great advances in the therapy of metastatic renal cell and urothelial carcinoma. Currently ICI are approved for the first-line therapy of cisplatin-unfit patients (Atezolizumab, Pembrolizumab) and second-line therapy in patients with metastasized urothelial cancer (Atezolizumab, Nivolumab, Pembrolizumab). For the therapy of metastasized RCC, Nivolumab is approved as a second-line therapy and in combination with the CTLA‑4 antibody Ipilimumab as a first-line therapy.What does the optimized radiological follow-up and therapy response assessment for ICI, which differ in their pathways from common chemotherapeutics and anti-angiogenetic drugs, look like? What strategies are needed to meet the upcoming challenges concerning interpretation of the acquired images?A systematic literature search was carried out for urothelial and renal cell carcinoma.Immune-related response criteria have been introduced to better characterize the imaging changes occurring under ICI, as monitoring response to immunotherapy still relies on RECIST.To properly identify and predict response after treatment with ICI, additional studies with long-term follow-ups are needed. Because of the growing use of ICI, radiologists and urologist should be familiar with common imaging findings (such as pseudo progress) under immunotherapy to correctly interpret these findings in daily routine.

Prostate cancer remains among the most commonly diagnosed malignancies worldwide in men. In patients with low-risk prostate cancer, the risk of metastasis and mortality is very low; therefore, a tumor surveillance strategy can be used. In patients undergoing active surveillance, curative active therapy is postponed without compromising opportunities for cure until there is evidence of progression or the patient desires active therapy. The aim of active surveillance in prostate cancer patients is to minimize treatment-related toxicity without impairing patient survival. To maintain patients under active surveillance, the following criteria should be met: prostate-specific antigen (PSA) ≤10 ng/ml, Gleason score ≤6, cT1 or cT2a, ≤2 biopsy cores with50% cancer involvement of every positive core. Follow-up in active surveillance patients is based on repeat biopsy, serial PSA measurements, and digital rectal examination.

Despite delays between diagnosis and surgery adversely affecting survival, patients frequently transfer their breast cancer care between institutions. This study was performed to assess the prevalence and effect of such transfers of care (TsOC) on the time to surgery, and its impact on current time-dependent breast cancer quality metrics at Commission on Cancer (CoC) and National Accreditation Program for Breast Centers (NAPBC)-accredited institutions.Patients having non-metastatic invasive breast cancer diagnosed between 2006 and 2015 at CoC and NAPBC centers ("reporting facilities") in the National Cancer Database were reviewed. TsOC refer to transferring into or out of a reporting facility between diagnosis and surgery.Among 622,793 patients, 36.6% of patients transferred care. TsOC add 7.3, 7.8, 8.7, and 9.8 days in time to surgery, chemotherapy, radiotherapy, and endocrine therapy, respectively (p's 0.0001). On multivariable analysis, the odds of surgery occurring 90 days from diagnosis were greatest for patients undergoing unilateral or bilateral mastectomy, Black or Hispanic patients, and those having TsOC (ORs 1.73, p's 0.0001). TsOC increase the odds of non-compliance, per patient, for chemotherapy, radiotherapy and endocrine therapy time-dependent measures by 65.4%, 25.6%, and 56.5%, respectively (p 0.0001).TsOC for newly diagnosed breast cancers to or from an accredited facility result in delays in time to surgery which can affect compliance with time-dependent quality measures. Facilities frequently receiving transferred patients may be most adversely affected. Although non-compliance with these quality measures is low, institutions and accrediting bodies should be aware of these associations in order to comply with time-dependent standards.

BACKGROUND: Identification of pathogenic germline alterations (PGAs) has important clinical and therapeutic implications in pancreas cancer. We performed comprehensive germline testing (GT) in an unselected prospective cohort of patients with exocrine pancreatic neoplasms with genotype and phenotype association to facilitate identification of prognostic and/or predictive biomarkers and examine potential therapeutic implications. METHODS: Six hundred fifteen unselected patients with exocrine pancreatic neoplasms were prospectively consented for somatic tumor and matched sample profiling for 410–468 genes. GT for PGAs in 76 genes associated with cancer susceptibility was performed in an “identified” manner in 356 (57.9%) patients and in an “anonymized” manner in 259 (42.1%) patients, using an institutional review board–approved protocol. Detailed clinical and pathological features, response to platinum, and overall survival (OS) were collected for the identified cohort. OS was analyzed with Kaplan-Meier curves. RESULTS: PGAs were present in 122 (19.8%) of 615 patients involving 24 different genes, including BRCA1/2, ATM, PALB2, and multiple additional genes associated with the DNA damage response pathway. Of 122 patients with germline alterations, 41.8% did not meet current guidelines for GT. The difference in median OS was not statistically significant between patients with and without PGA (50.8 months, 95% confidence interval = 34.5 to not reached, two-sided P = .94). Loss of heterozygosity was found in 60.0% of BRCA1/2. CONCLUSIONS: PGAs frequently occur in pancreas exocrine neoplasms and involve multiple genes beyond those previously associated with hereditary pancreatic cancer. These PGAs are therapeutically actionable in about 5% to 10% of patients. These data support routinely offering GT in all pancreatic ductal adenocarcimona patients with a broad panel of known hereditary cancer predisposition genes.

The complex fluid-structure interaction problem associated with the flow of blood through a heart valve with flexible leaflets is investigated both experimentally and numerically. In the experimental test rig, a pulse duplicator generates a pulsatile flow through a biomimetic rigid aortic root where a model of aortic valve with polymer flexible leaflets is implanted. High-speed recordings of the leaflets motion and particle image velocimetry measurements were performed together to investigate the valve kinematics and the dynamics of the flow. Large eddy simulations of the same configuration, based on a variant of the immersed boundary method, are also presented. A massively parallel unstructured finite-volume flow solver is coupled with a finite-element solid mechanics solver to predict the fluid-structure interaction between the unsteady flow and the valve. Detailed analysis of the dynamics of opening and closure of the valve are conducted, showing a good quantitative agreement between the experiment and the simulation regarding the global behavior, in spite of some differences regarding the individual dynamics of the valve leaflets. A multicycle analysis (over more than 20 cycles) enables to characterize the generation of turbulence downstream of the valve, showing similar flow features between the experiment and the simulation. The flow transitions to turbulence after peak systole, when the flow starts to decelerate. Fluctuations are observed in the wake of the valve, with maximum amplitude observed at the commissure side of the aorta. Overall, a very promising experiment-vs-simulation comparison is shown, demonstrating the potential of the numerical method.

Aims/hypothesis Diabetes has a major negative effect on intensive care unit outcome. This has been partly attributed to impaired respiratory neuromuscular function. However, data on respiratory neuromuscular involvement in diabetes are lacking. This study therefore aimed to assess respiratory neuromuscular function related to diabetic polyneuropathy in patients with type 2 diabetes. Methods Respiratory neuromuscular function was assessed by the use of volitional tests and twitch mouth (TwPmo) and twitch transdiaphragmatic (TwPdi) pressures during non-volitional bilateral anterior magnetic phrenic nerve stimulation in 21 male type 2 diabetic patients without pulmonary disease and in 23 healthy, well-matched controls (forced expiratory volume in 1 s 103±11 vs 103±12% predicted; p=0.9). Results Both volitionally assessed maximal inspiratory and expiratory mouth pressures, and sniff nasal and transdiaphragmatic pressures were comparable between diabetic patients and controls (p>0.1 for all). TwPmo was reduced in diabetic patients compared with controls (1.3±0.5 vs 1.0± 0.4 kPa; p=0.04), while TwPdi was comparable (1.7±0.5 vs 1.6±0.7 kPa; p=0.6). Following subgroup analysis, patients with no or mild polyneuropathy (n=10) as assessed by neurological disability scoring had normal respiratory neuromuscular function, whereas patients with moderate or severe polyneuropathy (n=11) presented with markedly impaired respiratory neuromuscular function as indicated by TwPmo (1.3±0.4 vs 0.8±0.3 kPa; p=0.01) and TwPdi (1.9±0.6 vs 1.1±0.4 kPa; p

Ischemic stroke, caused by embolism of cerebral vessels, inflicts high morbidity and mortality. Endovascular aspiration of the blood clot is an interventional technique for the recanalization of the occluded arteries. However, the hemodynamics in the Circle of Willis (CoW) are not completely understood, which results in medical misjudgment and complications during surgeries. In this study we establish a multiscale description of cerebral hemodynamics during aspiration thrombectomy. First, the CoW is modeled as a 1D pipe network on the basis of computed tomography angiography (CTA) scans. Afterwards, a vascular occlusion is placed in the middle cerebral artery and the relevant section of the CoW is transferred to a 3D computational fluid dynamic (CFD) domain. A suction catheter in different positions is included in the CFD simulations. The boundary conditions of the 3D domain are taken from the 1D domain to ensure system coupling. A Eulerian-Eulerian multiphase simulation describes the process of thrombus aspiration. The physiological blood flow in the 1D and 3D domains is validated with literature data. Further on, it is proved that domain reduction and pressure coupling at the boundaries are an appropriate method to reduce computational costs. Future work will apply the developed framework to various clinical questions.

Objective In general, the pharmacokinetics (PK) of antibiotics in intensive care unit (ICU) patients are known to differ from healthy subjects. These differences can pose challenges in developing appropriate dosing guidelines. The primary objective of this report was to characterize the disposition of levofloxacin in critically ill patients and to assess any relationships between patient covariates and the PK parameters. Methods 20 patients in the ICU were given levofloxacin, 500 mg, as an i.v. infusion for a half hour. Plasma samples were taken until 24 hours and assayed using HPLC. The concentration-time data were analyzed using population analysis with NONMEM. Results The data were described using a 2-compartment model. Creatinine clearance was determined to be a statistically significant predictor of variability in total levofloxacin clearance. For patients with higher levofloxacin clearance, the resulting efficacy for different strains of bacteria (expressed as free AUC/MIC ratios) suggested that for less sensitive pathogens, a dosage adjustment may be needed. Conclusion A model describing the pharmacokinetics of levofloxacin in critically ill patients was developed. It was determined that creatinine clearance has a significant role in the disposition of levofloxacin. This may have significant implications in the clinical setting for identifying optimal dosage regimens for ICU patients.

It has been shown that left ventricular assist devices (LVADs) increase the survival rate in end-stage heart failure patients. However, there is an ongoing demand for an increased quality of life, fewer adverse events, and more physiological devices. These challenges necessitate new approaches during the design process. In this study, computational fluid dynamics (CFD), lumped parameter (LP) modeling, mock circulatory loops (MCLs), and particle image velocimetry (PIV) are combined to develop a numerical Pump Testing Framework (nPTF) capable of analyzing local flow patterns and the systemic response of LVADs. The nPTF was created by connecting a CFD model of the aortic arch, including an LVAD outflow graft to an LP model of the circulatory system. Based on the same geometry, a three-dimensional silicone model was crafted using rapid prototyping and connected to an MCL. PIV studies of this setup were performed to validate the local flow fields (PIV) and the systemic response (MCL) of the nPTF. After validation, different outflow graft positions were compared using the nPTF. Both the numerical and the experimental setup were able to generate physiological responses by adjusting resistances and systemic compliance, with mean aortic pressures of 72.2-132.6 mm Hg for rotational speeds of 2200-3050 rpm. During LVAD support, an average flow to the distal branches (cerebral and subclavian) of 24% was found in the experiments and the nPTF. The flow fields from PIV and CFD were in good agreement. Numerical and experimental tools were combined to develop and validate the nPTF, which can be used to analyze local flow fields and the systemic response of LVADs during the design process. This allows analysis of physiological control parameters at early development stages and may, therefore, help to improve patient outcomes.

The jet of the outflow cannula is a potential risk for patients undergoing cardiopulmonary bypass (CPB), because increased jet velocities lead to altered flow conditions and might furthermore mobilize atherosclerotic plaques from calcified aortas. The cannula jet is therefore among the main reasons for cerebral hypoxia and stroke in CPB patients. In the past, we developed a validated computational fluid dynamics (CFD) model to analyze flow conditions during CPB as dependent on cannulation and support modalities. This model is now applied to develop a novel CPB outflow cannula to reduce the jet effect and increase cerebral blood flow. The Multi-Module Cannula (MMC) is based on a generic elbow cannula that was iteratively improved. It features an inner wall to smoothly guide the blood as well as an elliptically shaped outlet diffuser. During standard CPB conditions of 5 L/min, the pressure drop over the MMC is 61 mm Hg, compared with 68 mm Hg with a standard cannula. The maximum velocities are decreased from 3.7 m/s to 3.3 m/s. In the cannula jet of the MMC, the velocities are reduced further, down to 1.6 m/s. The cerebral blood flow is typically reduced during CPB. Using the MMC, however, it reaches almost physiological values at 715 mL/min. These results suggest that the MMC outperforms standard CPB cannulas. Further design improvements and improved insertion techniques are under consideration.

Iodine deficiency still exists in many countries worldwide, to a certain degree this is also true for Germany. Food of animal origin can be a good source for iodine depending on the feed. To investigate the possible use of laying hen feed enriched with iodine, we conducted a feeding experiment with 40 laying hens receiving feed with different amounts of iodine either as KIO3 or in the form of seaweed. Iodine concentration in eggs increased significantly depending on iodine intake after a 2 week period. Seaweed could also be used as an iodine source by the hens. A subsequent consumption study with 24 volunteers showed that eggs enriched with iodine can increase human's iodine excretion and therefore improve human's iodine supply. This new strategy is thought to accompany salt iodization programs, not to replace them.

Peri- or postoperative neurological complications are among the main risks for patients undergoing extracorporeal circulatory support (ECC). Two of the main reasons are an increased risk for strokes and altered flow conditions leading to cerebral hypoperfusion. This is strongly affected by cerebral autoregulation, which is the body's intrinsic ability to provide sufficient cerebral blood flow (CBF) despite changes in cerebral perfusion pressure (CPP). This complex mechanism has been mainly neglected in numerical studies, which have often been applied for analysis of ECC. In this study, a mathematical model is presented to implement cerebral autoregulation into computational fluid dynamics (CFD) studies. CFD simulations of cardiopulmonary bypass (CPB) were performed in a 3D model of the cardiovascular system, with flow variations between 4.5-6 L/min. Cerebral outlets were modeled using an equation to calculate CBF based on CPP. Assuming full regulation, CBF was kept constant for CPP between 80 and 120 mm Hg. A deviation in CBF of 20% occurred for CPP between 55-80 mm Hg and 120-145 mm Hg, respectively. The level of regulation was varied to take possible impairment of cerebral autoregulation into account. Furthermore, chronic hypertension was modeled by increasing the baseline CPP. Results indicate that even for full autoregulation, CBF is decreased during CPB. It is even lower for impaired autoregulation and hypertensive patients, demonstrating the strong impact of autoregulation on CBF. It is therefore imperative to include this mechanism into CFD studies. The presented model can help to improve CPB support conditions based on patient-specific autoregulation parameters.

Understanding circulatory autoregulation is essential for improving physiological control of rotary blood pumps and support conditions during cardiopulmonary bypass (CPB). Cerebral autoregulation (CAR), arguably the most critical, is the body's intrinsic ability to maintain sufficient cerebral blood flow (CBF) despite changes in aortic perfusion pressure. It is therefore imperative to include this mechanism into computational fluid dynamics (CFD), particle image velocimetry (PIV), or mock circulation loop (MCL) studies. Without such inclusions, potential losses of CBF are overestimated. In this study, a mathematical model to mimic CAR is implemented in a MCL- and PIV-validated CFD model. A three-dimensional model of the human vascular system was created from magnetic resonance imaging records. Numerical flow simulations were performed for physiological conditions and CPB. The inlet flow was varied between 4.5 and 6 L/min. Arterial outlets were modeled using vessel-specific, flow-dependent cerebrovascular resistances (CVRs), resulting in a variation of the pressure drop between 0 and 80mmHg. CBF is highly dependent on the level of CAR during CPB. By varying the CVR parameters up to the beginning of plateau phase, it can be regulated between 0 and 80% of physiological CBF. So while implementing autoregulation, CBF remains unchanged during a simulated native cardiac output of 5L/min or CPB support of 6L/min. Neglecting CAR, constant backflow from the brain occurs for some cannula positions. Using flow-dependent CVR, CBF returns to its baseline at a rate of recovery of 0.25s. Results demonstrate that modeling of CAR by flow-dependent CVR delivers feasible results. The presented method can be used to optimize physiological control of assist devices dependent upon different levels of CAR representing different patients.

Postoperative erectile dysfunction (ED) is one of the potential after-effects of radical prostatectomy. The aim of this study was to learn which caregivers inform the patients prior to the intervention about the risk of ED, which individuals the patients discuss this issue with, and whether the patients preoperatively consider use of a PDE5 inhibitor for proerectile therapy after the operation.Using the IIEF-5 questionnaire, the preoperative erectile function of 110 patients was evaluated after the hospital admission interview. The patients were asked who had informed them about the risk of postoperative ED. They were also asked in whom they had confided to discuss this issue and whether they were prepared to undergo postoperative proerectile therapy with a PDE5 inhibitor. The patients were subsequently assigned to one of two groups: group I, consisting of those with a preoperative IIEF scoreor = 21, or group II, those with a preoperative IIEF score21.The answers given by groups I and II did not differ significantly. The median patient age was the same, 68, in both groups. In addition to being informed about postoperative ED by the hospital doctor on admission (100%), the patients were informed about this by the following individuals (results for group II in parentheses): board-certified urologist, 81.8% (74%); general practitioner (GP), 27.3%; partner, 12.1% (11.7%); self-help groups, 0% (2.6%); and friends, 3% (6.5%). Patients also discussed the risk of postoperative ED with the following individuals (results for group II in parentheses): local urologist, 66.7% (63.4%); partner, 45.5% (42.9%); hospital doctor, 39.4% (42.9%); GP, 21.2% (23.4%); friends, 9.1% (14.3); or no one, 3% (5.2%). Regarding whether patients were willing to undergo postoperative therapy using a PDE5 inhibitor, 36.4% in group I and 32.5% in group II said yes, 12.1% in group I and 11.7% in group II said no, and 51.5% in group I and 55.8% in group II were undecided.Irrespective of the patient's erectile status, the hospital doctor and the local urologist informed the patients about the risk of postoperative ED. Satisfactory information delivered by at least two people occurred in over 70% of all cases. The most frequent confidant of the patient for discussing this issue was his local urologist. Fewer than 50% of the patients discussed this topic with their partners. Possible reasons for underestimating the importance of sexual function could be the frequent taboo status of sexuality as a discussion topic in relationships, as well as preoperative distress. These circumstances should be taken into account by offering sufficient information, including that on the availability of postoperative proerectile therapy, for both the patient and his partner as early as possible, i.e., at the stage of choosing a treatment option.

Mandibuloacral dysplasia (MAD) is a syndrome characterized by partial lipodystrophy and a distinct phenotype, which includes progressive osteolysis of the mandible and clavicles, cutaneous atrophy, joint contractures, and diabetes mellitus. We now describe the results of hyperinsulinemic glucose clamps performed in conjunction with indirect calorimetry in two subjects with MAD. At a glucose level of 5 mmol/L and insulin concentration of over 6.5 x 10(4) pmol/L, glucose disposal rates were less than 20% of maximum insulin-stimulated glucose disposal in five nondiabetic controls. Basal hepatic glucose output was elevated in the two patients and was incompletely suppressed by a 1200 mU/m2.min infusion of insulin. Glucose and lipid oxidation rates were inappropriately elevated, reflecting marked hypermetabolism. Pharmacological concentrations of insulin failed to normally suppress lipid oxidation, diminish FFA levels, or adequately suppress glucagon levels. In summary, MAD is a unique form of lipodystrophic diabetes characterized by typical somatic features, extreme insulin resistance, and marked hypermetabolism.

Restructured nursing roles resulting from innovative professional practice models and participative governance systems create a demand for new and expanded competencies. The impact for nursing staff development is the concurrent requirement to develop programs that match the skill/competency requirements of nurses in emerging practice models. This article recounts how one nursing department implemented a learning needs assessment (LNA) process as a means of integrating staff development into professional nursing practice.

Prostate cancer (PCA) is the most frequent onlocological disease in men. Every year there are ca. 202.000 new cases of prostate cancer in Europe. Curative treatment of this carcinoma via brachytherapy is becoming increasingly significant (20-30% of all curative approaches). Initial staging and thus allocation to risk groups prior to the commencement of therapy is esspecially important for successful brachytherapy treatment.Low-dose-rate (LDR) brachytherapy (i.e. SEED implantation) distinguishes itself both with respect to the procedure as well as the indication from high-dose-rate brachytherapy (afterloading procedure). Both treatment procedures are employed as monotherapy as well as in combination with external radiation.LDR monotherapy is reported to achieve biochemically relapse-free outcome of up to 90% in low-risk tumours during 10-year follow-up periods. Combined HDR tele- and brachytherapy is reported to achieve a biochemically relapse-free outcome of 80-90% with intermediate- and high-risk tumours in long-term follow-up.While randomized studies are as yet missing, it is still possible to derive the following application algorithms from monitoring studies and cohort studies: application of LDR monobrachytherapy must be restricted to low-risk tumorus. Combined HDR tele- and brachytherapy can be sucessfully applied in cases of intermediate- and high-risk tumours. The outcome depends significantly on the initial, pre-therapy PSA value and Gleason score. Posttherapeutically, the nadir value is crucial with respect to predicting the biochemically relapse-free outcome.

Cabanas, working 30 years ago, was the first to use the term "sentinel lymph node" in urology. His definition of the sentinel lymph node was based on typical anatomical patterns and therefore could not do justice to any individual variability in lymphatic drainage. This meant that application of the technique yielded high false-negative rates, and because of this it was largely abandoned. Dynamic visualization of lymphatic drainage by blue dye in melanoma patients resulted in a renaissance of the sentinel node concept in penile cancer in the mid-1990s. With constant improvements and standardization of the technique it proved possible to reduce the incidence of false-negative results from the initial 22% to 4.8%. This technique requires that specialists in urology, pathology, and nuclear medicine collaborate closely, and high standards are also essential in quality control.

Germany and several other countries are areas of severe iodine deficiency. In addition to iodized salt additional strategies to fight iodine deficiency exist. A promising possibility is the supplementation of feed with iodine, in order to increase its content in food of animal origin. In a feeding experiment 24 male castrated and female piglets of the cross breed Deutsche Landrasse x Pietrain were fed a high iodine supplemented diet. At a body weight of 100 kg the animals were slaughtered and the effect of the iodine supplementation on iodine content in the organs was studied. Animals receiving 30 mg iodine/kg feed showed significantly higher iodine contents in muscle, heart, kidney, liver, serum, fat and in the thyroidea than animals receiving no iodine supplementation. The iodine content in muscle and organs increased by a factor three to seven. Concerning meat quality and other slaughter parameters there was no difference between the two groups. This demonstrates that this strategy is in addition to iodized salt a possibility to reduce iodine deficiency.

Eye surgery is performed under local anesthesia in more than 90% of the cases. While injecting the local anesthetics a deep sedation is desired. During surgery however the patient should be cooperative, such as to avoid inadvertent movements. We routinely perform local anesthesia (retrobulbar injection and van Lint block) under intravenous anesthesia with propofol (Disoprivan) and ketamine (Ketalar, Ketanest).To control safety and efficacy of this method a prospective study was performed including 100 consecutive patients. The results were to be compared with an earlier study where 35 Patients received midazolam (Dormicum) and alfentanil (Rapifen) as sedation. The actual protocol included the following points: 1. Personal judgement of the patient. 2. Conditions to perform the retrobulbar injection, 3. Intraoperative conditions and additional sedation, 4. Pulse, blood pressure and blood oxygen concentration, 5. Complications95% of the patients had a total amnesia of the injection of local anesthetics. Retrobulbar injection is comfortable (96%), but may be difficult in patients with a narrow orbit and exotropia (4%). Intraoperative conditions were noted as good in 97%. Additional sedation during surgery was necessary in 3%. Blood pressure and pulse remained stable. Blood oxygen concentration showed a tendency to sink during intravenous anesthesia. This could be managed easily by additional oxygen via face mask if necessary. Postoperative emesis was noted in 3%. No further ocular complications occurred that might be related to the anesthetic management. In an earlier study including 35 Patients under comparable conditions we used midazolam and alfentanil for sedation. The results were similar. Midazolam and alfentanil were then used in over 2000 operations. Often the patients were deeply sedated and asleep during surgery which meant a potential risk of a sudden awakening and moving the head inadvertently. Occasionally paradoxical reactions occurred after midazolam.Using propofol and ketamine while performing the local anesthesia the patients are awake but relaxed and cooperative during surgery. This method has now been used routinely in over 1000 cases. It has proved to be clinically safe and efficient. It offers the surgeon good working conditions and is well tolerated by the patients, reducing their preoperative and perioperative anxieties.

Trends in classification usage were analyzed through examination of all issues of Mental Retardation, American Journal of Mental Deficiency, and American Journal on Mental Retardation from 1980 through 1989. The research was undertaken to determine whether the recommendations by Taylor (1980) and MacMillan, Meyers, and Morrison (1980) regarding subject description had been implemented. Results indicated that the system of the American Association on Mental Retardation (previously the American Association on Mental Deficiency) was used in over 50% of the articles, whereas the American Educators system was used in only 10%. A further analysis regarding the use of various classification systems as a function of the age of the subjects was also conducted. Implications of these results were discussed.

Patients selected for the presence of scleroderma-related antibodies (anti-DNA-topoisomerase I [anti-topo I; n = 43], anticentromere antibody [ACA; n = 63], or anti-Pm-Scl [n = 12]) were studied for class I and class II major histocompatibility complex antigens, as well as for Gm and Km allotypes. Anti-topo I was associated with HLA-DR5 (70% of patients versus 30.6% of controls; Pcorr = 0.0018, relative risk [RR] = 5.3). All patients with anti-Pm-Scl were positive for HLA-DR3 (versus 23.5% of controls; Pcorr less than 0.001); 6 of these patients were DR3/4 heterozygous (50% versus 3.5% of controls; Pcorr less than 0.001, RR = 27.3). Patients with ACA were frequently positive for HLA-DR1, DR4, or DRw8, with 73.7% demonstrating at least 1 of these alleles (versus 41.2% of controls; Pcorr = 0.0152, RR = 4.0). This group of ACA-positive patients who had DR1, DR4, and/or DRw8 consisted mainly of a subgroup of patients with rheumatoid arthritis. We conclude that different class II major histocompatibility complex antigens influence the formation of anti-topo I and anti-Pm-Scl. Important clinical differences between these patient groups and the immunogenetic heterogeneity support the notion of different antibody-defined scleroderma subsets.

Glucocorticoids increase GHRH-stimulated GH secretion when added in vitro to cultured monkey, rat, and human pituitary cells and when injected in vivo into anesthetized rats. Yet, in man glucocorticoids inhibit linear growth and GH secretion. To clarify this apparent disparity and to determine if glucocorticoid stimulation can augment GH release in man after direct pituitary stimulation with GHRH, we administered 1 microgram/kg GHRH dosage to seven normal men before and after a 4-day course of prednisone (20 mg, orally, three times daily). The second GHRH test was done 12 h after the last dose of prednisone was given. Prednisone significantly inhibited the mean maximal increase in serum GH after GHRH treatment [20.7 +/- 4.5 (+/- SE) vs. 6.3 +/- 2.4 micrograms/L; P less than 0.01] as well as the GH value obtained by summing and averaging the individual means of the 15, 30, 45, 60, 75, and 90 min serum GH concentrations (11.1 +/- 1.2 vs. 4.3 +/- 0.9 micrograms/L; P less than 0.05). The mean serum insulin-like growth factor I and plasma glucose concentrations were not significantly altered by prednisone administration. These results together with previous in vitro findings imply that glucocorticoid-induced inhibition of GH secretion in man does not occur at the level of the pituitary gland, but, rather, at the hypothalamus or above.

Fenoprofen calcium (2,400 mg/day) or aspirin (3,900 mg/day) was administered in double-blind fashion to 20 rheumatoid patients during 6 months of gold induction therapy, and to 20 rheumatoid patients not receiving gold. Among both the gold-treated and nongold-treated patients, the fenoprofen and aspirin groups improved equally in all but one parameter of disease activity. Fenoprofen and aspirin did not differ significantly in the observed prevalences of abdominal discomfort, guaiac-positive stools, or peptic ulcers. Aspirin was associated with significantly higher mean serum glutamic oxaloacetic transaminase (SGOT) levels than fenoprofen, but only among patients undergoing gold induction. Comparison of efficacy parameters between patients treated with gold and patients treated with oral drugs alone revealed significant differences favoring gold.

Two tests were developed for the rapid identification of Cryptococcus neoformans based on pigment produced by the organism's phenoloxidase activity. Caffeic acid was incorporated into cornmeal agar, a medium used routinely for yeast identification. When tested on this medium, only C. neoformans isolates produced brown pigment. All other yeasts maintained their normal morphology and did not produce the reaction product. A non-medium-based test was developed for same-day identification of C. neoformans isolates. Paper strips saturated with a buffered L-beta-3,4-dihydroxyphenylalanine-ferric citrate solution were inoculated with isolates and incubated at 37 degrees C. Pigment production occurred only with C. neoformans isolates, many within 60 to 90 min. All other yeasts remained negative.

The acute metabolic effects of 20,000-dalton human growth hormone (hGH20K) in man have not previously been tested. We compared changes in concentrations of free fatty acids (FFA), glucose, and insulin in nine growth hormone deficient children following injection of 22,000-dalton intact human growth hormone (hGH22K) and the smaller variant, hGH20K. There was a significant decline (37%) in the mean FFA concentration from baseline to 1/2 hour post-injection and from baseline to 1 hour post-injection (36%) in the children given hGH22K, but no such decline was seen after injection of hGH20K. No significant differences in mean insulin or glucose concentrations were noted between the two treatment groups, and glucose and insulin concentrations did not acutely change after injection of either hormone. The results of this study indicate that hGH20K has a diminished activity for suppression of FFA as compared to hGH22K. This suggests that GH residues 32-46, missing in hGH20K, constitute all or part of the region of hGH22K producing this response, or that the different primary structures of the two hormones result in tertiary structural differences and altered biological activity.

• A double-blind crossover study to determine the effects on intraocular pressure (IOP) and blood pressure of topically instilled 0.125% and 0.25% solutions of clonidine hydrochloride by comparison with a 2% pilocarpine hydrochloride solution and placebo was carried out in a total of 21 patients with open-angle glaucoma, each of whom received a single drop of each preparation in the same glaucomatous eye on separate days. Both clonidine solutions were effective in lowering the IOP; the 0.25% solution was more effective than the 0.125% solution, and the former was slightly less potent than pilocarpine. Pupil diameter was essentially unchanged in all but one of the patients after clonidine. Pilocarpine reduced pupil diameter in all patients. One eye treated with placebo also showed a reduction in pupil size. Both systolic and diastolic blood pressure showed a statistically significant reduction after clonidine, but the magnitude of the change was small. We do not regard the minor blood pressure changes as being a threat to the optic nerve but further studies in this aspect of topical clonidine therapy are required. ( Arch Ophthalmol 95:1368-1373, 1977)

Recurrent angio-oedema with eosinophilic dermatitis is characterized by the following symptoms: persistent hypereosinophilic, episodes of angio-oedema, urticarial papular and papulo-pustular exanthema, episodes of fever, as well as increased IgE and IgM levels. Eosinophilic dermatitis with subcorneal pustulation can be seen on histological examination. This disease should be distinguished from the classical hypereosinophilic syndrome because of the absence of internal symptoms and because the prognosis is apparently favourable. Internal corticosteroids are the therapy of choice.

An automated method for lactat determination on centrifugal analyser is described. The measurements have been done by end-point method during 300 seconds. A reagent blank is introduced in each run and its absorbance is deduced from those of the tests. The suitability of the method is assessed, particularly the sensitivity (detection limit) and the accuracy by checking the recovery. The results obtained by the automated and the manual method are well correlated.

In vitro assays of human neutrophil phagocytosis, adherence, enzyme release, and response to chemotactic factors were utilized to determine the effects of benoxaprofen on these cells. At concentrations of 30 and 300 micrograms/ml benoxaprofen partially inhibited phagocytosis without affecting adherence. High concentrations (300 micrograms/ml) of benoxaprofen, but not aspirin or gold, enhanced the release of the granular enzymes beta-glucuronidase and lysozyme, but not the release of the cytoplasmic enzyme lactic dehydrogenase from both resting and phagocytosing neutrophils. High concentrations (300 micrograms/ml) of benoxaprofen also inhibited the response of neutrophils to chemotactic factors as determined by both the leading front and leukotactic index methods. These unique in vitro effects of this antiinflammatory agent are compatible with recent clinical reports concerning its efficacy and toxicity.

Leprosy and tuberculosis are chronic infectious diseases causing major global health problems, for which no effective control by vaccination has been achieved. Recent advances in biotechnology may facilitate the design of a new vaccine generation. In this paper the need for, and the potential of, leprosy and tuberculosis vaccines are discussed.

A new tricyclic antidepressant, doxepin, was evaluated for its ability to block the amine uptake mechanism of the peripheral adrenergic neuron and blood platelet in man. At low doses, there was no evidence of inhibition of the amine pump. However, at moderate doses (200–300 mg/day), necessary for effective antidepressant activity, doxepin was found to inhibit the pressor responses to tyramine and to reduce platelet 5-HT. These studies indicate that doxepin is a less potent inhibitor of the amine pump in the peripheral adrenergic neuron and blood platelet than is DMI or protriptyline. Doxepin, at the antidepressant dose level does alter biogenic amine uptake, an effect consistent with the biogenic amine hypothesis of depression. However, at 300 mg/day, a dose which blocks the pressor response to tyramine, antagonism of the antihypertensive effects of guanethidine and related drugs was demonstrated.

Iprindole is a clinically effective antidepressant similar to other tricyclic drugs in structure. In animal studies it does not appear to inhibit the levarterenol membrane pump. Investigation was made of iprindole's effect on the peripheral adrenergic levarterenol pump in man utilizing blood pressure response to tyramine and levarterenol. Other clinically effective tricyclic drugs exert, by blocking its uptake, a potent blocking effect on the blood pressure response to tyramine and, in a similar manner, augment the pressor response to infused levarterenol. In contrast, iprindole showed no significant effect on tyramine and levarterenol blood pressure response. Other tricyclics also reduce platelet serotonin content, probably by inhibiting membrane uptake of this amine. Iprindole failed to alter platelet serotonin content. These findings call into question that aspect of the biogenic amine theory of depression which states that the tricyclic drugs exert their antidepressant action by inhibiting the membrane pump.