Interval Of Several Weeks Research Articles

Impact of the time interval between biopsy and radical prostatectomy on functional outcomes

PurposeThe aim of our study was to investigate the impact of the time interval between prostate biopsy and radical prostatectomy (RP) on postoperative urinary continence (UC)/erectile function (EF). From a clinical point of view, an interval of several weeks seems to facilitate surgical preparation.Materials and methodsWe retrospectively analyzed patients who underwent RP for localized prostate cancer (PCa) in a tertiary care center between 2011 and 2020. We evaluated the influence of the following variables on UC and EF 1 year after RP: time from biopsy to RP, age, BMI, pathological T-stage, EF and intraoperative nerve sparing (unilateral vs. bilateral). For this purpose, we performed linear regression analyses as well as manual grouping and cluster analyses to identify possible temporal cutoff ranges. The EPIC-26 and the IIEF questionnaires were used for the assessment of UC and EF.ResultsWe identified 6202 consecutive patients who underwent RP. Neither manual grouping nor cluster analyses showed a significant difference in continence or potency after RP. According to linear regression models, only age was an independent predictor of incontinence (95%-CI 0.006–0.01), and EF before RP (95%-CI 0.22–0.26), age (95%-CI – 0.68 to – 0.5), BMI (95%-CI – 0.66 to – 0.29) and bilateral NS (95%-CI 5.5–2.1) had significant impacts on postoperative EF (all p < 0.001).ConclusionIn the selected patient population, the time interval between prostate biopsy and RP did not seem to have an effect on postoperative functional outcomes (UC and EF).

Characterization of Large Brain Metastases with 18F-Fluciclovine PET/CT Treated with Staged Stereotactic Radiosurgery (SSRS): Phase 1 Proof-of-Concept Interim Analysis

Single-session stereotactic radiosurgery (SRS) for large brain metastases (>2cm) results in modest local control. Temporally staged SRS (SSRS), whereby 2 stages of SRS are delivered over a time interval of several weeks, is a novel strategy associated with improved control rates and acceptable radiation necrosis rates. Biomarkers for response are lacking. Here, we report interim results of a phase 1, proof-of-concept study (NCT04689048) to assess the potential clinical utility of amino acid radiotracer 18F-fluciclovine PET/CT as a functional integral biomarker for patients with large brain metastases treated with SSRS. Patients with previously untreated large brain metastases (≥1 lesion; >2cm) underwent a baseline (pre-treatment) 18F-fluciclovine PET/CT and contrast-enhanced treatment planning brain MRI immediately before first SSRS (15 Gy), an interim PET/CT + MRI (4 weeks after the 1st SSRS, immediately prior the 2nd SSRS [15 Gy]), and post-treatment PET/CT + MRI (8 weeks after 2nd SSRS). This interim analysis reviewed the imaging characteristics from static PET images acquired 10-25 minutes after 18F-fluciclovine injection, for the first 7 enrolled patients who completed baseline imaging and 5 who completed the entire treatment course. Seven patients completed baseline imaging and were treated with SSRS for 9 protocol-eligible target lesions, and an additional 25 bystander lesions were treated with SRS. The median age was 72 years and 57% were female. All lesions > 5 mm exhibited baseline increased 18F-fluciclovine uptake compared to the normal contralateral brain. The median baseline target lesion diameters and volumes were 2.16 cm (1.76-3.22 cm) and 4.71cc (2.24-10.21 cc). The median baseline SUVmax, SUVpeak, and SUVmean values were 5.78 (2.16-8.79), 3.33 (0.5-2.72), and 1.75 (1.22-5.16), respectively. The median relative reduction in diameter and volume were both 2% (-13% to 23% and -30% to 60%, respectively) at the interim scans, and at the first follow-up were 30% (-0.2% to 44%) and 43% (-13% to 94%), respectively. Corresponding median relative reduction values for SUVmax, SUVpeak, and SUVmean at interim scans were 20% (-174%-73%), 9% (-99% to 75%), and 14% (-36% to 69%), and at first follow-up 59% (21% to 87%), 41% (-11% to 86%), and 21% (-44% to 79%), respectively. Bystander lesions (< 2 cm) treated with SRS had a median baseline lesion diameter and volume of 0.5 cm (Range: 0.20-1.64 cm) and 0.06 cc (Range: 0.01-1.94 cc). Corresponding median reductions for SUVmax were 5% at interim and 63% at follow-up scans. This proof-of-concept interim study reports baseline 18F-fluciclovine metrics for patients with brain metastases of varying lesion diameters and volumes. Target lesions appear to demonstrate interval reduction in PET metrics after SSRS, more than dimensional measurements alone.

Methods and Tips for Intravenous Administration of Adeno-associated Virus to Rats and Evaluation of Central Nervous System Transduction.

Adeno-associated virus (AAV) vectors are a key reagent in the neurosciences for clustered regularly interspaced short palindromic repeats (CRISPR), optogenetics, cre-lox targeting, etc. The purpose of this manuscript is to aid the investigator attempting expansive central nervous system (CNS) gene transfer in the rat via tail vein injection of AAV. Wide-scale expression is relevant for conditions with widespread pathology, and a rat model is significant due to its greater size and physiologic similarities to humans compared to mice. In this example application, a wide-scale neuronal transduction is used to mimic a neurodegenerative disease that affects the entire spinal cord, amyotrophic lateral sclerosis (ALS). The efficient wide-scale CNS transduction can also be used to deliver therapeutic protein factors in pre-clinical studies. After a post-injection expression interval of several weeks, the effects of the transduction are evaluated. For a green fluorescent protein (GFP) control vector, the amount of GFP in the cerebellum is estimated quickly and reliably by a basic imaging program. For motor disease phenotypes that are induced by the ALS related protein transactive response DNA-binding protein of 43 kDa (TDP-43), the deficits are scored by escape reflex and rotarod. Beyond disease modeling and gene therapy, there are diverse potential applications for the wide-scale gene targeting described here. The expanded use of this method will aid in expediting hypothesis testing in the neurosciences and neurogenetics.

Donepezil Does Not Enhance Perceptual Learning in Adults with Amblyopia: A Pilot Study.

Amblyopia is a developmental disorder that results in a wide range of visual deficits. One proven approach to recovering vision in adults with amblyopia is perceptual learning (PL). Recent evidence suggests that neuromodulators can enhance adult plasticity. In this pilot study, we asked whether donepezil, a cholinesterase inhibitor, enhances visual PL in adults with amblyopia. Nine adults with amblyopia were first trained on a low-contrast single-letter identification task while taking a daily dose (5 mg) of donepezil throughout training. Following 10,000 trials of training, participants showed improved contrast sensitivity for identifying single letters. However, the magnitude of improvement was no greater than, and the rate of improvement was slower than, that obtained in a previous study in which six adults with amblyopia were trained using an identical task and protocol but without donepezil (Chung et al., 2012). In addition, we measured transfer of learning effects to other tasks and found that for donepezil, the post-pre performance ratios in both a size-limited (acuity) and a spacing-limited (crowding) task were not significantly different from those found in the previous study without donepezil administration. After an interval of several weeks, six participants returned for a second course of training on identifying flanked (crowded) letters, again with concurrent donepezil administration. Although this task has previously been shown to be highly amenable to PL in adults with amblyopia (Chung et al., 2012; Hussain et al., 2012), only one observer in our study showed significant learning over 10,000 trials of training. Auxiliary experiments showed that the lack of a learning effect on this task during donepezil administration was not due to either the order of training of the two tasks or the use of a sequential training paradigm. Our results reveal that cholinergic enhancement with donepezil during training does not improve or speed up PL of single-letter identification in adults with amblyopia, and importantly, it may even halt learning and transfer related to a crowding task.Clinical Trial Registration: This study was registered with ClinicalTrials.gov (NCT03109314).

Efficient in vivo transfection and safety profile of a CpG-free and codon optimized luciferase plasmid using a cationic lipophosphoramidate in a multiple intravenous administration procedure

As any drug, the success of gene therapy is largely dependent on the vehicle that has to selectively and efficiently deliver therapeutic nucleic acids into targeted cells with minimal side-effects. In the case of chronic diseases that require a life-long treatment, non-viral gene delivery vehicles are less likely to induce an immune response, thereby allowing for repeated administration. Beyond the gene delivery efficiency of a given vector, the nature of nucleic acid constructs also has a central importance in gene therapy protocols.Herein, we investigated the impact of two firefly luciferase encoding plasmids on the transgene expression profile following systemic delivery of lipoplexes in mice, as well as their potential to be safely and efficiently readministered. Whereas pTG11033 plasmid is driven by a strong ubiquitous cytomegalovirus promoter, pGM144 plasmid, which has been designed to avoid inflammation and provide sustained transgene expression in lungs, is CpG-free and is under control of the human elongation factor-1 alpha promoter.Combined to the efficient cationic lipophosphoramidate BSV4, bioluminescence data showed that both plasmids were mostly expressed in the lungs of mice following a primary injection of lipoplexes. However, mice transfected with pGM144 exhibited a higher and more sustained transgene expression than those treated with pTG11033. Repeated administration studies revealed that several injections of lipoplexes could lead to similar transgene expression profiles if an interval of several weeks between subsequent injections was respected. A transient hepatotoxicity and a partial inflammatory response were caused by lipoplex injection, irrespective of the plasmid used.Altogether, these results indicate that repeated systemic administration of lipophosphoramidate-based lipoplexes in mice conducts to an effective lung transfection without serious side effects, and highlight the need to use long-lasting expressing and well tolerated plasmids in order to efficiently renew transgene expression by the successive doses.

Mechanisms underlying encoding of short-lived versus durable episodic memories.

We continuously encounter and process novel events in the surrounding world, but only some episodes will leave detailed memory traces that can be recollected after weeks and months. Here, our aim was to monitor brain activity during encoding of events that eventually transforms into long-term stable memories. Previous functional magnetic resonance imaging (fMRI) studies have shown that the degree of activation of different brain regions during encoding is predictive of later recollection success. However, most of these studies tested participants' memories the same day as encoding occurred, whereas several lines of research suggest that extended post-encoding processing is of crucial importance for long-term consolidation. Using fMRI, we tested whether the same encoding mechanisms are predictive of recollection success after hours as after a retention interval of several weeks. Seventy-eight participants were scanned during an associative encoding task and given a source memory test the same day or after ∼6 weeks. We found a strong link between regional activity levels during encoding and recollection success over short time intervals. However, results further showed that durable source memories, i.e., events recollected after several weeks, were not simply the events associated with the highest activity levels at encoding. Rather, strong levels of connectivity between the right hippocampus and perceptual areas, as well as with parts of the self-referential default-mode network, seemed instrumental in establishing durable source memories. Thus, we argue that an initial intensity-based encoding is necessary for short-term encoding of events, whereas additional processes involving hippocampal-cortical communication aid transformation into stable long-term memories.

Increased Risk of Bilateral Infection

Hypothesis: Simultaneous bilateral endoprosthetic total hip or knee arthroplasty (as in the current article) is in theory inevitably associated with an increased rate of bilateral infections. Reasoning: A department specific risk of infection due to surgery—for example, 5/1000—for endoprosthetic total hip or knee arthroplasty means that even for simultaneous bilateral surgery, such a risk of infection exists (if not even a higher risk, which we will not consider here). If one furthermore assumes that in case of surgery both surgical sites may be affected—the current article does not provide any information in this respect—then the risk of bilateral infection may be 5/1000 if all cases of infection are always bilateral or, for example, 5/10 000 if only one in 10 cases of infection is bilateral. In two-stage surgery (with an interval of several weeks between procedures) the risk per intervention is 5/1000. Both interventions combined have a risk of infection of 2×5/1000=10/1000 for an infection to affect one joint. The probability that in a two-stage procedure (with an interval of several weeks between procedures) both joints become infected is 5/1000×5/1000=25/1000 000. In order to be able better to balance these very divergent surgical risks it would be necessary to obtain detailed data on the bilateral proportion of infections in the group of patients having had simultaneous surgery. Unrelated to that, statistical probability in simultaneous bilateral surgery works against the surgeon, which is why I personally do not recommend this procedure to my patients.

How the Interval between Prime and Boost Injection Affects the Immune Response in a Computational Model of the Immune System

The immune system is able to respond more vigorously to the second contact with a given antigen than to the first contact. Vaccination protocols generally include at least two doses, in order to obtain high antibody titers. We want to analyze the relation between the time elapsed from the first dose (priming) and the second dose (boost) on the antibody titers. In this paper, we couple in vivo experiments with computer simulations to assess the effect of delaying the second injection. We observe that an interval of several weeks between the prime and the boost is necessary to obtain optimal antibody responses.

Long-Term Disease-Free Survival of Patients with AML Relapse After T-Cell-Depleted Allogeneic Stem Cell Transplantation by Re-Induction Therapy and Subsequent Interferon-Boosted Donor Lymphocyte Infusion

Abstract 3064Relapse of AML after allogeneic stem cell transplantation (alloSCT) has a very poor prognosis. Salvage re-induction chemotherapy leads to clinical remissions in a substantial number of patients, but these remissions tend to be of short duration. In contrast, donor lymphocyte infusions (DLI) have the potential to effect long-lasting remissions, but the interval of several weeks to months that is required to develop a DLI-induced anti-leukemia response may prevent efficient control of a highly proliferative leukemia. In addition, a high tumor burden may suppress the immune response. In contrast, the combination of efficient cytoreduction by chemotherapy with DLI administered in rapid succession under circumstances favoring the development of an early and profound immune response might have the potential to eradicate otherwise resistant leukemia cells. We therefore adopted an institutional therapeutic strategy for relapsed myeloid leukemia post-allogeneic SCT based on administration of DLI at the anticipated end of the neutropenic phase after salvage re-induction chemotherapy. At this time point, the high prevalence of a pro-inflammatory milieu should favor the induction of the immune response, and an expected state of lymphopenia should promote the expansion of infused T cells by homeostatic proliferation. If 3 weeks after DLI no graft versus host disease (GvHD) was observed, the potential anti-leukemia immune response was further amplified by treatment with interferon- α (IFN- α) until GvHD occurred.Between January 2000 and December 2009 44 patients with relapsed myeloid malignancy after alloSCT were treated at our hospital. Pre-transplant diagnoses were AML n=40, CMML n=1 and MDS n=3. Median time from SCT to relapse was 187 days. Median follow-up after relapse was 3.1 years. 5 patients had a smouldering relapse (<10% bone marrow blasts) and 39 patients had an overt relapse.Of 39 patients with overt relapse, 7 patients (18%) did not receive re-induction therapy due to poor performance status (n=5) or patient choice (n=2). 32 patients received remission-induction therapy consisting of gemtuzumab ozogamycin (n=9), cytosine arabinoside-containing chemotherapy (n=17), or both (n=6). Following this treatment, 7 of 32 patients had rapidly progressive disease during induction therapy (n=6) or died due to toxicity (n=1) and did not receive DLI.The remaining 25 patients received DLI at a dose of 5.0×10 ^6 CD3+ cells/kg for related and 2.5×10 ^6 CD3+ cells/kg for unrelated donors 3 weeks after the start of remission-induction therapy. In 16 of these patients DLI was boosted with IFN- α 3.0×10 ^6 IE once daily. This strategy resulted in acute GvHD in 17 of 25 patients (n=8 grade 1–2, n=9 grade 3–4). At 6 weeks after DLI, 16 patients had reached CR, 5 patients had failed to reach CR (2 with GvHD) and 4 suffered treatment-related mortality (3 with GvHD). Of the 16 patients in CR, 4 had no signs of GvHD and developed a second relapse during the follow-up period. Only 3 of 12 patients in CR with signs of acute GvHD at 6 weeks after DLI developed a second relapse. In total, 9 of 17 patients (53%) with acute GvHD after DLI had long term survival versus none without acute GvHD. During follow-up, 8 patients developed chronic GvHD (n=4 limited, n=4 extensive).Finally, 5 patients with an early detected smouldering relapse received DLI, which was boosted with IFN- α in 2 patients, without salvage re-induction therapy. All 5 patients developed GvHD (n=2 grade 1–2, n=3 grade 3–4) and 3 patients achieved a CR of whom 1 patient died from GvHD.Our results indicate that treatment of relapsed AML after alloSCT with salvage re-induction therapy followed by DLI at the end of the neutropenic phase during minimal residual disease, with additional boosting of the immune response with IFN- α, can result in long-term disease-free survival. Disclosures:Off Label Use: Interferon: DLI-boosting.

Iliopsoas Cyst Causing Persistent Pain After Total Hip Arthroplasty

Persistent pain after total hip arthroplasty (THA) has many potential causes. The most common are aseptic loosening, infection, and heterotopic ossification. Irritation of the iliopsoas tendon due to the acetabular component is an underestimated cause of persistent groin pain and functional disability after THA with rare incidence. Pain specific to iliopsoas tendonitis includes activities such as hyperextension of the hip, forced flexion, and activities of daily living (eg, ascending stairs). This article presents a case of a 50-year old man with clinical and radiological signs of osteoarthritis of the right hip joint. A THA was performed. After a symptom-free interval of several weeks postoperatively, the patient reported pain projecting from the right groin and radiating ventromedially along the leg. Magnetic resonance imaging of the hip showed a fluid-filled cyst in anatomical proximity to the femoral nerve causing an iliopsoas tendonitis. The patient underwent surgical resection of the cyst was performed by an anterior approach; a conjunction to the hip joint was not present. The implanted components of the prosthesis showed good osseointegration with no signs of loosening. The cyst was removed and the iliopsoas tendon was released. A few weeks after the operation, the patient was pain free. At 17-month follow-up, no problems were reported. In cases such as this, finding the correct diagnosis may be difficult and misleading. Conservative and operative therapeutic options are discussed and compared with divergent findings in the literature.

LH secretion and ovulation following exposure of Arctic charr to different temperature and photoperiod regimes: Responsiveness of females to a gonadotropin-releasing hormone analogue and a dopamine antagonist

The timing of ovulation and LH plasma levels were investigated in Arctic charr reared at 5°C and 10°C, exposed to the ambient photoperiod, or short or long-day photoperiod regimes during the prespawning period. The effectiveness of sGnRHa alone, or sGnRHa combined with a dopamine antagonist, in stimulating LH secretion and inducing ovulation was also investigated. With the natural photoperiod, ovulation occurred spontaneously at 5°C, but was inhibited at 10°C. A transition from 10 to 5°C soon resulted in suppression of the inhibition. At 5°C, the effectiveness of sGnRHa was similar to that of sGnRHa combined with pimozide in stimulating LH secretion and inducing ovulation. At 10°C, sGnRHa+pimozide was more effective that sGnRHa alone in stimulating LH secretion and inducing a high rate of ovulation, suggesting that dopamine-induced inhibition of LH secretion could occur naturally in Arctic charr at 10°C. Exposure of Arctic charr to a long day (LD) photoperiod regime in fall and winter did not completely inhibit ovulation, but markedly delayed it and prolonged the ensuing ovulation period. The LD photoperiod also reduced LH plasma levels in females while they were ovulating, but did not modify the responsiveness of the pituitary to GnRHa stimulation compared to a control group exposed to a short-day (SD) photoperiod. There was an interval of several weeks after a transition from LD to SD before LH secretion and ovulation were stimulated.

Delayed cardiac tamponade in a patient with previous minor blunt chest trauma

Hemopericardium with cardiac tamponade after non-penetrating chest trauma is a very rare but life-threatening condition. If this complication develops after an interval of several weeks following the non-penetrating chest trauma, the causal relation with the traumatic event is less evident, which may delay proper diagnosis and adequate treatment. We describe diagnosing and therapeutic management of a patient in shock who suffered from cardiac tamponade four weeks after a minor blunt chest trauma.

Early vs. Delayed Elective Laparoscopic-Assisted Colectomy in Sigmoid Diverticulitis: Timing of Surgery in Relation to the Acute Attack

The timing of elective surgery in acute sigmoid diverticulitis in relation to the acute attack is not clear. Early elective surgery during the same hospitalization as the acute attack or delayed surgery after an interval of several weeks are the options. This study was designed to evaluate the influence of timing on morbidity, conversion rate, histologic findings, and costs. A total of 178 patients with elective laparoscopic-assisted sigmoid resections for diverticulitis between 1997 and 2005 were retrospectively assessed; 77 patients underwent early and 101 delayed surgery. Outcomes were surgical morbidity, conversion rate, histologic findings, and financial impact of timing. The two groups showed no significant difference apart from a higher body mass index in the delayed group (25.5 vs. 26.6 kg/m2, P = 0.035). Surgical morbidity was not significantly different. Conversion rate was significantly higher in the early group (P < 0.001). Converted patients had an increased surgical morbidity of 23.8 vs. 19.1 percent (P = 0.323) and hospitalization was significantly longer (13.5 vs. 10.5 days; P < 0.001). Histology revealed inflammation in 75.3 percent in the early group compared with 23.8 percent in the delayed group. Total treatment costs were not different between groups, whereas total earnings were higher in the delayed group resulting in a lower hospital deficit. Early elective surgery in patients with acute sigmoid diverticulitis results in a higher conversion rate. If patients respond to initial antibiotic therapy, delayed colectomy after an interval of six weeks or more is recommended.

Electroencephalographic evidence for pre‐motor cortex activation during inspiratory loading in humans

Faced with mechanical inspiratory loading, awake animals and anaesthetized humans develop alveolar hypoventilation, whereas awake humans do defend ventilation. This points to a suprapontine compensatory mechanism instead of or in addition to the 'traditional' brainstem respiratory regulation. This study assesses the role of the cortical pre-motor representation of inspiratory muscles in this behaviour. Ten healthy subjects (age 19-34 years, three men) were studied during quiet breathing, CO2-stimulated breathing, inspiratory resistive loading, inspiratory threshold loading, and during self-paced voluntary sniffs. Pre-triggered ensemble averaging of Cz EEG epochs starting 2.5 s before the onset of inspiration was used to look for pre-motor activity. Pre-motor potentials were present during voluntary sniffs in all subjects (average latency (+/-s.d.): 1325 +/- 521 ms), but also during inspiratory threshold loading (1427 +/- 537 ms) and during inspiratory resistive loading (1109 +/- 465 ms). Pre-motor potentials were systematically followed by motor potentials during inspiratory loading. Pre-motor potentials were lacking during quiet breathing (except in one case) and during CO2-stimulated breathing (except in two cases). The same pattern was observed during repeated experiments at an interval of several weeks in a subset of three subjects. The behavioural component of inspiratory loading compensation in awake humans could thus depend on higher cortical motor areas. Demonstrating a similar role of the cerebral cortex in the compensation of disease-related inspiratory loads (e.g. asthma attacks) would have important pathophysiological implications: it could for example contribute to explain why sleep is both altered and deleterious in such situations.

Regeneration of the mammalian central vestibular pathway using the rat as animal model.

Regeneration of the mammalian central vestibular system was examined in rat. The lateral vestibulospinal tract (LVST) of infant rat was transected unilaterally at the level of C1-3. After a postoperative interval of several weeks, the LVST was examined by injecting an anterograde tracer (wheat germ agglutinin-conjugated horseradish peroxidase) into the lateral vestibular nucleus (LVN) and a retrograde tracer (Fast Blue) into the lumbar enlargement. More than half of the rats showed successful regeneration, indicating definite plasticity in the mammalian central vestibular system.

Geochronology and geochemistry of lavas from the 1996 North Gorda Ridge eruption

Radiometric dating of three North Gorda Ridge lavas by the 210Po– 210Pb method confirms that an eruption occurred during a period of increased seismic activity along the ridge during late February/early March 1996. These lavas were collected following detection of enhanced T-phase seismicity and subsequent ocean bottom photographs documented the existence of a large pillow mound of fresh-appearing lavas. 210Po– 210Pb dating of these lavas indicates that an eruption coinciding with this seismicity did occur (within analytical error) and that followup efforts to sample the recent lava flows were successful. Compositions of the three confirmed young lavas and eleven other samples of this contiguous “new flow” sequence are distinct from older lavas from this area but are variable at a level outside analytical uncertainty. These intraflow variations can not easily be related to a single, common parent magma. Compositional variability within the new flow is compared to that of other recently documented individual flow sequences, and this comparison reveals a strong positive correlation of compositional variance with flow volumes spanning a range of >2 orders of magnitude. The geochemical heterogeneity in the North Gorda new flow probably reflects incomplete mixing of magmas generated from a heterogeneous mantle source or from slightly different melting conditions of a single source. The compositional variability, range in sample ages (up to 6 weeks) and range in active seismicity (4 weeks) imply that this relatively large flow was erupted over an interval of several weeks.

An experience of treatment for patients with thoracic esophageal cancer invading adjacent organs.

The treatment of patients with thoracic esophageal cancer invading adjacent organs is controversial. The effect, on survival, of esophagectomy with regional node dissection after combined chemotherapy and radiotherapy was studied in six patients with the esophageal cancer. Two patients undergoing esophagectomy survived > 39 months without relapse. Postoperative complications were not observed in patients undergoing esophagectomy with a two-step surgical procedure (interval of several weeks between esophagectomy and reconstruction), while complications were observed in all patients undergoing a one-stage surgical procedure. Two-step esophagectomy with regional node dissection after combined chemo- and radiotherapy is a promising option for patients with esophageal cancer invading adjacent organs.

Continent reconstruction of detrusor hyperreflexia by sacral bladder denervation combined with continent vesicostomy

We describe a two-stage surgical procedure for complex hyperreflexic detrusor dysfunction refractory to conservative therapy. First, ventral and dorsal sacral rhizotomies (S2 to S4/5) are performed to restore vesical storage function and abolish autonomic dysreflexia. Then, after an interval of several weeks to allow for detrusor relaxation, continent vesicostomy is performed for suprapubic clean intermittent catheterization. The procedure is effective both objectively and subjectively, is only moderately invasive, and requires neither sophisticated nor expensive medical equipment.

Immobilization-related hypercalcaemia—a possible novel mechanism and response to pamidronate

Immobilization-related hypercalcaemia is an uncommon but important condition being associated not infrequently with both urolithiasis and osteoporosis. In this study 5 patients who had been immobilized for a mean of 3 months and had a mean adjusted serum calcium of 3.15 mmol/l were treated with doses of intravenous pamidronate ranging between 10 mg and 45 mg. All patients became normocalcaemic by day 3. Patients 1-3 mobilized shortly after treatment and remained normocalcaemic. In those patients who continued to be immobile hypercalcaemia recurred after an interval of several weeks. Retreatment with pamidronate again resulted in normocalcaemia. No side effects were noted with treatment. All of the patients studied had increased rates of bone resorption as shown by elevated urinary hydroxyproline/creatinine ratios (median:range) of 0.101:0.045-0.180 (normal less than 0.033) and elevated calcium/creatinine ratios of 2.50:0.69-3.63 (normal less than 0.50). None of the patients in this study had any of the usual risk factors for developing immobilization-related hypercalcaemia though all 5 patients had problems with significant sepsis which we postulate may have lead to cytokine release which in turn contributed to the development of hypercalcaemia. We conclude that pamidronate (at doses as low as 10 mg) is safe and effective in immobilization-related hypercalcaemia and suggest that sepsis should be added to the list of risk factors for development of this syndrome.

Reproducibility of cerebral glucose utilization measured by PET and the [18F]-2-fluoro-2-deoxy-d-glucose method in resting, healthy human subjects

The stability of cerebral glucose utilization was examined in nine right-handed, healthy men (age, 24.88 +/- 2.93 years) using positron emission tomography (PET) and the [18F]-fluorodeoxglucose (FDG) method. Each study was run twice at intervals of 1-12 weeks with the subject at rest. The average cerebral metabolic rate for glucose (CMRGlu) was 5.40 +/- 0.71 mg/100 g per min (coefficient of variance, 13.08). The average intraindividual variation of CMRGlu was 7.91% +/- 15.46% (P = 0.13). Metabolic indices (MI: regional/mean cortical CMRGlu) were used to determine the regional cerebral metabolic distribution. The interindividual (coefficient of variance, 7.13) and intraindividual variabilities (average variation, -0.12% +/- 8.76%) of MI were smaller than those of metabolic rates. No reproducible significant asymmetry was observed. The FDG method used with subjects at rest thus yields low intraindividual variability of both cerebral glucose consumption and regional metabolic distribution, even at an interval of several weeks. Cerebral glucose utilization measured under such conditions may act as a reliable reference for determination of the influences of physiological (activation), pharmacological or pathological processes on cerebral glucose metabolism.