Metabolic evaluation of patients with recurrent idiopathic calcium nephrolithiasis

BACKGROUND: Metabolic evaluation in recurrent idiopathic calcium renal stone-formers (RCSF) was analysed with respect to the following questions: (1) do three 24-h urines provide more diagnostic accuracy in the metabolic evaluation of RCSF than 1 or 2 urines?; (2) does time after stone event influence the diagnostic yield?; (3) is urine composition at weekends different from that at mid-week?; (4) what are the prevalences of the most important risk factors (RF) of idiopathic calcium nephrolithiasis, i.e. low volume (LV), hypercalciuria (HC), hyperoxaluria (HO), hyperuricosuria (HU), hypocitraturia (Hypo-Cit), and hypomagnesiuria (Hypo-Mg)?; and (5) do male RCSF differ from females with respect to urinary RFs? METHODS: Seventy-five RCSF (59 men, 16 women) collected three 24-h urines (U1-3) while on free-choice diet. To account for possible variations in lifestyle and diet, U1 and U3 had to be collected midweek and U2 at a weekend. RESULTS: When considering all three urines together (U1 + U2 + U3), the number of RF abnormalities/patient was 2.8 +/- 0.1, higher than numbers of any combination of two urines or of any single urine (P = 0.0001 for all comparisons). The number of RF abnormalities also rose with time after stone event, from 0.8 +/- 0.1 (range 0-4) in U1 to 1.1 +/- 0.1 (range 0- 4) in U3 (P = 0.011 vs U1). Whereas all other RF did not change between collections, urine volume was lower in U2 (1793 +/- 90 ml) than in U1 (2071 +/- 97 ml, P = 0.0001 vs U2) and U3 (1946 +/- 97 ml, P = 0.046 vs U2). At least 1 abnormality was found in 85.3% of all RCSF, and multiple abnormalities occurred in 47%. The most frequent RF was HC (39%), followed by HO and LV (32% each), Hypo-Cit (29%), HU (23%) and Hypo-Mg (19%). Males more often had Hypo-Cit (P < 0.001) and Hypo-Mg (P < 0.01) than females, whereas HO was more frequent in female RCSF (P < 0.025 vs males). CONCLUSIONS: Diagnostic accuracy of metabolic evaluation in RCSF increases both with the number of urines collected and the time passing after a stone event. Urines collected at weekends differ from those of the week only by their lower volumes. Abnormalities of RF for calcium nephrolithiasis can be detected in 85.3% of RCSF, and HC is the most common RF both in male and female RCSF.      

The presence of an HLA-identical sibling donor has no impact on outcome of patients with high-risk MDS or secondary AML (sAML) treated with intensive chemotherapy followed by transplantation: results of a prospective study of the EORTC, EBMT, SAKK and GIMEMA Leukemia Groups (EORTC study 06921).

This report used the framework of a large European study to investigate the outcome of patients with and without an HLA-identical sibling donor on an intention-to-treat basis. After a common remission-induction and consolidation course, patients with an HLA-identical sibling donor were scheduled for allogeneic transplantation and patients lacking a donor for autologous transplantation. In all, 159 patients alive at 8 weeks from the start of treatment were included in the present analysis. In total, 52 patients had a donor, 65 patients did not have a donor and in 42 patients the availability of a donor was not assessed. Out of 52 patients, 36 (69%) with a donor underwent allogeneic transplantation (28 in CR1). Out of 65 patients, 33 (49%) received an autograft (27 in CR1). The actuarial survival rates at 4 years were 33.3% (s.e. = 6.7%) for patients with a donor and 39.0% (s.e. = 6.5%) for patients without a donor (P = 0.18). Event-free survival rates were 23.1% (s.e. = 6.2%) and 21.5% (s.e. = 5.3%), respectively (P = 0.66). Correction for alternative donor transplants did not substantially alter the survival of the group without a donor. Also, the survival in the various cytogenetic risk groups was not significantly different when comparing the donor vs the no-donor group. This analysis shows that patients with high-risk myelodysplastic syndrome and secondary acute myeloid leukemia may benefit from both allogeneic and autologous transplantation. We were unable to demonstrate a survival advantage for patients with a donor compared to patients without a donor.     

In vivo measurement of the shear modulus of the human vocal fold: interim results from eight patients

The shear modulus of the vocal fold is an essential parameter required to enhance our understanding of how the vocal fold operates, to develop mathematical models of phonatation, and to provide benchmarks to quantify the effectiveness of surgical procedures. The authors announced the successful deployment of an instrument to measure vocal fold elasticity in vivo last year, and now present the data taken from eight patients in vivo. The shear modulus was measured at the mid-membranous point, in a transverse direction with respect to the axis drawn between the anterior commissure and vocal process. The range of mean shear modulus results is 701–2,225 Pa, with a mean value of 1,371 Pa.     

Pelvic pain and recurrent urinary incontinence after laparoscopic colposuspension with the endo-stapler

Laparoscopic colposuspension is one of many new operations for treating female urinary stress incontinence. With initially reported success rates similar to those of the traditional open procedure, it appears to combine the advantages of laparoscopy (such as minimal invasiveness and quicker return to normal activities) with the effectiveness of the standard procedure. Different methods and approaches are used, but endoscopic suture techniques remain difficult and time-consuming. The use of endostapling devices for fixation of alloplastic material has been a tempting alternative. We present a case during which laparoscopic colposuspension was performed using staples and mesh. Incontinence did not improve, and the patient suffered severe chronic pain for 18 months postoperatively. Removal of the alloplastic material and traditional abdominal resuspension led to complete cure.     

Rapid chemical kinetic techniques for investigations of neurotransmitter receptors expressed in Xenopus oocytes

Xenopus laevis oocytes have been used extensively during the past decade to express and study neurotransmitter receptors of various origins and subunit composition and also to express and study receptors altered by site-specific mutations. Interpretations of the effects of structural differences on receptor mechanisms were, however, hampered by a lack of rapid chemical reaction techniques suitable for use with oocytes. Here we describe flow and photolysis techniques, with 2-ms and 100-μs time resolution, respectively, for studying neurotransmitter receptors in giant (≈20-μm diameter) patches of oocyte membranes, using muscle and neuronal acetylcholine receptors as examples. With these techniques, we find that the muscle receptor in BC₃H1 cells and the same receptor expressed in oocytes have comparable kinetic properties. This finding is in contrast to previous studies and raises questions regarding the interpretations of the many studies of receptors expressed in oocytes in which an insufficient time resolution was available. The results obtained indicate that the rapid reaction techniques described here, in conjunction with the oocyte expression system, will be useful in answering many outstanding questions regarding the structure and function of diverse neurotransmitter receptors.     

Monitoring during resuscitation

Use of many different types of monitors during resuscitation has been described in the literature. These monitors differ in their usefulness, technical feasibility, initial costs, and long-term costs (Table 4). There have been many published reports of CPR success rates in the hospital and in the pre-hospital setting. In spite of considerable advances in technology over the past 30 years, survival from CPR has changed little over that time. Although numerous types of monitoring during resuscitation are possible, and sometimes useful, the impact of expensive technology on ultimate outcome (survival) must be critically evaluated.     

An analysis of invasive airway management in a suburban emergency medical services system

INTRODUCTION: Airway management is the most critical and potentially life-saving intervention performed by emergency medical service (EMS) providers. Invasive airway management often is required in non-cardiac-arrest patients who are combative or otherwise uncooperative. The success of prehospital invasive airway management in this patient population was evaluated. METHODS: A retrospective review was undertaken of the records of all such patients requiring endotracheal intubation over a three-year period (1987-1989). The study population included 278 patients enrolled by five advanced life support (ALS) units serving a suburban population of 425,000. Field trip sheets were reviewed for diagnosis, intubation method and success, number of intubation attempts, provider experience, reasons for unsuccessful intubations, and complications. RESULTS: A total of 394 invasive airway management attempts were performed on 278 patients. The overall successful intubation rate was 75% (41% orotracheal, 52% nasotracheal, 7% other or unknown). The most common diagnoses were COPD and pulmonary edema (30%) and trauma (24%). Experienced providers were successful on the first attempt in 57% of cases compared to 50% by inexperienced providers (p=.24). Multiple intubation attempts were required in 33% of the patients. There was no statistically significant difference in success rates between the orotracheal and nasotracheal methods (p=.51). The most common reason for unsuccessful intubation was altered level of consciousness. Complications occurred with 7% of successful attempts and in 18% of unsuccessful attempts (p less than .001). Forty-six percent of the patients who were not intubated successfully in the field and required intubation in the emergency department (ED) received a neuromuscular blocking agent prior to successful intubation. CONCLUSION: Prehospital providers can intubate a high but improvable proportion of non-cardiac-arrested patients by both the orotracheal and nasotracheal routes. The use of pharmacologic adjuncts to facilitate the prehospital intubation of selected, non-cardiac-arrested patients is a promising adjunct that needs further evaluation.     

The "motion-blind" patient: low-level spatial and temporal filters

The "motion-blind" patient previously described by Zihl et al. (1983) was investigated using standard psychophysical procedures with stimuli whose spatial and temporal properties could be separately manipulated. Detection experiments for sinewave grating stimuli of varying spatial and temporal frequency showed sensitivity in this patient to be only slightly impaired. Temporal integration for stimuli of varying spatiotemporal frequency exhibited the expected space-time covariation seen in normal vision. An examination of the suprathreshold discriminative capacity of this patient was undertaken for spatial frequency, contrast, and temporal frequency. Although all of these discriminative functions were impaired, those concerning temporal frequency or velocity were dramatically reduced. No similar loss was seen for spatial frequency discrimination for moving or temporally varying stimuli. No measurable temporal frequency discrimination was present above 6 Hz and no velocity discrimination above 6 degrees/sec. Experiments involving the direction discrimination of suprathreshold drifting gratings of arrays of random dots revealed an inability to perceive direction of movement above a velocity of about 6 degrees/sec. Contrast thresholds contingent on direction of motion of a drifting grating also showed a much greater deficit than simple detection. Apparent motion using 2-flash random dot kinematograms revealed that the residual motion vision of this patient corresponded to the "short-range" motion process of normal vision. This process originally defined by Braddick (1974) operates over restricted space and time intervals. Apparent motion could only be supported by a narrow range of intermediate spatial displacements. These results suggest that this patient does exhibit some residual motion perception, probably corresponding to a severely impaired "short-range" mechanism. The patient's relatively intact ability to perform simple types of discrimination but severe impairment of performance at making judgments relevant to the nature of motion of the same stimuli suggests that while the components necessary for the analysis of motion are intact their more global associations have been disrupted. This implicates an extrastriate locus of the brain damage. Alternative explanations for the nature of the deficit are discussed.     

Influence of transcranial magnetic stimulation on the execution of memorised sequences of saccades in man

Memorised sequences of saccades are cortically controlled by the supplementary motor area (SMA), as shown in animal experiments and in humans with isolated SMA lesions. We applied transcranial magnetic stimulation (TMS) in eight healthy subjects executing memorised sequences of saccades. Sequences of three targets were presented. Then, upon a go-signal, the subjects had to execute the appropriate sequences. Ten to fifteen sequences were performed in each experiment, and the number of errors were counted. The number of errors increased significantly if TMS was given 80 ms before or 60 ms after the go-signal, with the stimulation coil overlying the SMA. There was no significant increase in errors if different stimulation intervals were chosen (160ms and 120ms before the go-signal; 100 ms, 140 ms or 240 ms after the go-signal), if the coil was positioned inappropriately (e.g. over the occipital cortex), or if the stimulator output was too low. We conclude that TMS can interfere specifically with the function of the SMA during a critical time interval close to the go-signal.     

The need for a novel generation of vaccines

Although empirical vaccine development was highly successful, it has now reached its limits. Vaccines are only efficacious against those pathogens which are primarily controlled by antibodies. Protection against many infectious agents, however, strongly depends on T lymphocytes. Thus, novel vaccines have to stimulate the combination of T lymphocytes that is required for an optimum protective immune response. Although identification of antigens remains crucial, novel vaccine design also needs to consider the best way of introducing these antigens to the immune system. Intracellular antigen compartmentalisation, the early cytokine milieu and the appropriate surface expression of co-stimulatory molecules are of major relevance for understanding how novel vaccines could induce a protective immune response mediated by T lymphocytes. Intracellular bacteria are controlled by T lymphocytes and efficacious vaccines against these pathogens are not available yet. In this treatise, two experimental vaccination strategies will be described in more detail. These encompass recombinant vaccine carriers expressing, and naked DNA constructs encoding, heterologous antigens. Both vaccination strategies proved to be protective in the model of experimental listeriosis of mice.