Contrasting effects of propranolol on sympathetic nerve activity and vascular resistance during orthostatic stress.

BACKGROUND. Previous studies in humans advanced the concept that cardiac filling pressure and contractility, the primary determinants of ventricular mechanoreceptor discharge, are important determinants of sympathetic outflow during orthostatic stress. Thus, intravenous propranolol greatly attenuated forearm vasoconstrictor response to venous pooling with lower body negative pressure (LBNP). The aim of this study was to reevaluate the experimental support for this concept by using direct measurements of sympathetic nerve activity. METHODS AND RESULTS. In 11 healthy humans, we recorded muscle sympathetic nerve activity (MSNA) with microelectrodes (peroneal nerve), as well as blood flow in the forearm and calf (venous occlusion plethysmography) at baseline and during graded LBNP. The same experiments were repeated after administration of propranolol (0.15 mg/kg i.v.), which is thought to decrease ventricular mechanoreceptor discharge. The major new findings are that propranolol neither increased baseline MSNA nor attenuated the increases in MSNA during graded orthostatic stress even though in the same subjects, propranolol simultaneously increased the baseline level of vascular resistance in both the forearm and calf and substantially attenuated the increases in regional vascular resistance during orthostatic stress. CONCLUSIONS. Systemic beta-blockade causes a marked dissociation between sympathetic outflow and vascular resistance that invalidates the use of intravenous propranolol as an experimental model to examine the reflex effects of ventricular mechanoreceptors on peripheral vascular resistance in humans.     

Classical and anaplastic seminoma: difference in survival

Classical and anaplastic seminoma are traditionally treated with radiation therapy and are said to have the same prognosis. A retrospective study was undertaken of 90 seminoma patients treated with radiation therapy between 1961 and 1985. The classical group consisted of 71 patients of whom 50 had stage I and 21 had stage II disease. The anaplastic group consisted of 19 patients of whom ten had stage I and nine had stage II disease. The median follow-up time was 64 months for the entire group. The 10-year relapse-free survival rate for the classical group was 94% and for the anaplastic group was 70% (P less than .05). For patients with classical stage I disease, the relapse-free actuarial survival rate was 98%; for patients with anaplastic stage I disease, it was 64% (P less than .02). For the classical stage II disease group, the relapse-free actuarial survival rate was 84% and for the anaplastic stage II disease group, 75% (P less than .70). Four patients in the classical group (6%) had relapses; of these, one patient had local recurrence of tumor, and three had distant metastases. In the anaplastic group, four patients (21%) had relapses; two patients had local recurrence of tumor, and two had distant metastases. Therefore the data suggest a difference in survival and relapse rates between classical and anaplastic seminoma.     

Dynamic muscular endurance in primary fibromyalgia compared with chronic myofascial pain syndrome.

The objective of the study was to quantify the voluntary dynamic muscular endurance (DME) in patients with primary fibromyalgia (PF) since easy fatigability of muscles is one of the major symptoms in this syndrome. Consecutive outpatients referred to a rheumatology clinic specializing in PF were investigated. Thirty-six patients with PF were compared with 18 patients with chronic myofascial pain (CMP) syndrome. Subjects were matched according to gender, age, height, weight, peak torque, and contractional work. The DME was defined as the number of repeated knee extensions necessary for the contractional work in two successive knee extensions to be equal to or below 70% of the initial value measured with an isokinetic dynamometer. A significantly lower DME was found in the PF group than in the CMP group: 11 (7-13) and 18 (11-25), respectively (median and quartiles), p less than .005. Patients with PF have a low voluntary muscular endurance compared to CMP patients.     

Small cell lung cancer in Norway. Should more patients have been offered surgical therapy?

OBJECTIVE: The final outcome of patients with small cell lung cancer (SCLC) is poor with an overall 5-year survival rate of less than 10%. Therefore, the question of surgery in patients with a technically-operable solitary tumor has been raised. The purpose of this study was to identify the proportion of patients with operable SCLC and to assess the prognosis of different treatment strategies. For patients who were operated, we compared the resection specimens from patients with more than 5-year survival with those with shorter survival to see whether the specimens belonged to different subclasses of SCLC. METHODS: In Norway all clinical and pathologic departments submit reports on cancer patients to the Cancer Registry. The Registry also has a law-regulated authority to collect supplemental information regarding diagnosis, treatment and outcome for all cancer patients from the hospitals in charge. All reports on patients diagnosed as having SCLC in limited disease or unknown stage during the time interval 1993-1999 were reviewed. Patients with a T2-tumor, in whom a pneumonectomy would have to be performed, were classified as potentially operable. Five-year relative survival was calculated for patients diagnosed in 1993-1997. RESULTS: During the actual period 2442 individuals with SCLC were identified. The majority was treated with conventional chemotherapy or concurrent chemoradiotherapy while 38 underwent surgical therapy. Following reclassification of 697 patients reported to have limited disease or unknown stage 180 were judged to be in stage I. In addition to the 38 resected patients 14 were considered fit for surgery technically and medically while 97 were found to be potentially operable treatment modalities apart from surgery yielded a 5-year survival rate <7%. For stage I (N=96) the rate was 11.3% in conventionally treated patients compared to 44.9% for those who underwent surgical resection. By pathological review of surgical specimens a diagnosis of SCLC was confirmed in all patients treated by surgery in the groups with long and short survival. CONCLUSION: This investigation demonstrates that patients with SCLC having a peripherally located tumor should be referred to surgery, as long time survival is far better than for conventionally treated patients.     

Functional correlates of verbal memory deficits emerging during nicotine withdrawal in abstinent adolescent cannabis users.

BACKGROUND: Cannabis remains the most widely used illicit substance by adolescents and is typically consumed by this population in the context of ongoing tobacco use. Human studies have shown that both cannabis and tobacco exert effects on cognitive function; however, little is known about possible interacting effects of these drugs on brain function and cognition during adolescent development. METHODS: Verbal learning and memory were assessed in 20 adolescent users of tobacco and cannabis and 25 adolescent tobacco users with minimal history of cannabis use. Functional magnetic resonance imaging was used to examine brain function and functional connectivity while a subset of these subjects performed a verbal working memory task. RESULTS: Delayed recall of verbal stimuli deteriorated during nicotine withdrawal among cannabis users but not among comparison subjects. During high verbal working memory load, nicotine withdrawal selectively increased task-related activation of posterior cortical regions and was associated with disruption of frontoparietal connectivity in adolescent cannabis users relative to comparison subjects. CONCLUSIONS: These observations suggest that cannabis use during adolescent development may disrupt neurocircuitry supporting verbal memory formation and that deficits associated with disruption of these neurocircuits are unmasked during nicotine withdrawal.     

Results of pulmonary resection for lung cancer in Norway, patients older than 70 years.

OBJECTIVE: Surgical resection for lung cancer is the mainstay of curative treatment, but studies regarding postoperative results and long term outcome in the elderly have differed. The purpose of the present study was to assess the early and long-term results of surgical resection in patients more than 70 years of age. METHODS: In Norway all clinical and pathologic departments submit reports on cancer patients to the Cancer Registry of Norway. This investigation included all patients more than 70 years of age resected for lung cancer in the time period 1993-2000. For results of long-time follow-up only patients operated on between 1993 and 1998 were included. RESULTS: A total of 763 patients (541 men) were identified aged 71-87 years. Postoperative mortality rate was 9%, highest after bilobectomy and pneumonectomy. The most commonly reported causes of postoperative death were pneumonia and cardiac complications. The majority of patients had tumor categorized as clinical stage (cStage) Ia and Ib. More than 100 in each of these groups proved to have more advanced disease postoperatively (pStage). The 5-year relative survival rate was significantly better in patients with disease in pStage I compared to higher stages. Women had a significantly better 5-year survival rate compared to men, 62.8 and 35.7%, respectively. CONCLUSIONS: Lung cancer surgery appears to be a relatively safe procedure even in the elderly. There is a high postoperative mortality after bilobectomy and pneumonectomy. However, when old people survive the postoperative period the long term prognosis seems favorable.