The state of general surgery training: a different perspective.

BACKGROUND: Much has been written about the influences of Accreditation Council for Graduate Medical Education (ACGME) work restrictions, the litigious climate in American medicine, and the proliferation of subspecialty fellowships on general surgery training. Few previous studies have addressed general surgical residents' perceptions of surgical training on a national level. METHODS: A 38-question Institutional Review Board-approved survey was sent via e-mail to the program directors at all ACGME-approved general surgical training programs for distribution to categorical general surgery residents. Voluntary responses to statements focusing on job satisfaction, quality of life, and the influences of operative experience, work hours, fellows, physician extenders, as well as faculty and administration on resident training were solicited. RESULTS: Overall, 997 responses were received from residents of all clinical levels from 40 states. Most respondents were from university-based programs (79%) with a broad representation of program sizes (mean of 6 graduates per year; range 2 to 11). Residents believe that they will be prepared to enter clinical practice at the conclusion of their training (86%), that the duration of surgical training is adequate (85%), and that they are exposed to sufficient case volume and complexity (85% and 84%, respectively). Only 360 respondents (36%) believe that they are financially compensated appropriately. Although most respondents support the ACGME work-hour restrictions (70%), far fewer feel that they improve their training or patient care (46.6% and 46.8%, respectively). Most respondents are proud to be surgical residents (88%), view surgery as a rewarding profession (87%), and would choose surgery as a profession again (77%). CONCLUSIONS: Surgical residents are positive regarding the quality of their training and life, although they feel poorly compensated for their work. Most residents intend to pursue fellowship training. Survey responses were consistent irrespective of gender, ethnicity, and program type.

Risk of malignancy in resected cystic tumors of the pancreas < or =3 cm in size: is it safe to observe asymptomatic patients? A multi-institutional report.

Recent international consensus guidelines propose that cystic pancreatic tumors less than 3 cm in size in asymptomatic patients with no radiographic features concerning for malignancy are safe to observe; however, there is little published data to support this recommendation. The purpose of this study was to determine the prevalence of malignancy in this group of patients using pancreatic resection databases from five high-volume pancreatic centers to assess the appropriateness of these guidelines. All pancreatic resections performed for cystic neoplasms < or =3 cm in size were evaluated over the time period of 1998-2006. One hundred sixty-six cases were identified, and the clinical, radiographic, and pathological data were reviewed. The correlation with age, gender, and symptoms (abdominal pain, nausea and vomiting, jaundice, presence of pancreatitis, unexplained weight loss, and anorexia), radiographic features suggestive of malignancy by either computed tomography, magnetic resonance imaging, or endoscopic ultrasound (presence of solid component, lymphadenopathy, or dilated main pancreatic duct or common bile duct), and the presence of malignancy was assessed using univariate and multivariate analysis. Among the 166 pancreatic resections for cystic pancreatic tumors < or =3 cm, 135 cases were benign [38 serous cystadenomas, 35 mucinous cystic neoplasms, 60 intraductal papillary mucinous neoplasms (IPMN), 1 cystic papillary tumor, and 1 cystic islet cell tumor], whereas 31 cases were malignant (14 mucinous cystic adenocarcinomas and 13 invasive carcinomas and 4 in situ carcinomas arising in the setting of IPMN). A greater incidence of cystic neoplasms was seen in female patients (99/166, 60%). Gender was a predictor of malignant pathology, with male patients having a higher incidence of malignancy (19/67, 28%) compared to female patients (12/99, 12%; p < 0.02). Older age was associated with malignancy (mean age 67 years in patients with malignant disease vs 62 years in patients with benign lesions (p < 0.05). A majority of the patients with malignancy were symptomatic (28/31, 90%). Symptoms that correlated with malignancy included jaundice (p < 0.001), weight loss (p < 0.003), and anorexia (p < 0.05). Radiographic features that correlated with malignancy were presence of a solid component (p < 0.0001), main pancreatic duct dilation (p = 0.002), common bile duct dilation (p < 0.001), and lymphadenopathy (p < 0.002). Twenty-seven of 31(87%) patients with malignant lesions had at least one radiographic feature concerning for malignancy. Forty-five patients (27%) were identified as having asymptomatic cystic neoplasms. All but three (6.6%) of the patients in this group had benign disease. Of the patients that had no symptoms and no radiographic features, 1 out of 30 (3.3%) had malignancy (carcinoma in situ arising in a side branch IPMN). Malignancy in cystic neoplasms < or =3 cm in size was associated with older age, male gender, presence of symptoms (jaundice, weight loss, and anorexia), and presence of concerning radiographic features (solid component, main pancreatic duct dilation, common bile duct dilation, and lymphadenopathy). Among asymptomatic patients that displayed no discernable radiographic features suggestive of malignancy who underwent resection, the incidence of occult malignancy was 3.3%. This study suggests that a group of patients with small cystic pancreatic neoplasms who have low risk of malignancy can be identified, and selective resection of these lesions may be appropriate.

Human leukocyte antigen-DRB1 position 11 residues are a common protective marker for sarcoidosis.

Genetic factors, in particular human leukocyte antigens (HLAs) are important determinants of susceptibility to sarcoidosis, a chronic granulomatous disease of undetermined etiology. To clarify the role of HLA in sarcoidosis we determined HLA-DR and -DQ alleles in case-control samples from three European populations (United Kingdom, Czech, and Polish) and compared these results with those published for three additional populations (Italian, Japanese, and Scandinavian) to determine whether the HLA-DR and/or -DQ alleles act as ethnic-dependent, or ethnic-independent modifiers of disease risk. Although variations were apparent in the alleles associated with susceptibility, reductions in the frequency of alleles associated with protection were remarkably consistent in the six populations. Previously detected associations between single-nucleotide polymorphisms at the TAP2 locus and sarcoidosis were shown to be due to linkage disequilibrium with the HLA-DR locus. The protective HLA-DR alleles, which encode the DR1 and DR4 antigens, were found to share characteristic small hydrophobic residues at position 11, which were replaced by small hydrophilic residues in the remaining, nonprotective, HLA-DR alleles. This residue position is within a pocket of the HLA-DR complex antigen binding groove (designated P6), where it is the only variable amino acid and therefore determines the peptide binding preferences of this pocket. A highly significant reduction in the frequency of individuals carrying HLA-DR alleles with a hydrophobic residue at position 11 was observed in the sarcoidosis cases in the three populations we examined. This suggests this HLA-DR residue is an important protective marker in sarcoidosis.

Sarcoidosis: genes and microbes--soil or seed?

Sarcoidosis is a multi-organ granulomatous disorder that is characterised by the accumulation of CD4+ T-lymphocytes resulting in a Th-1 type immune response. Although our understanding of the immune response in sarcoidosis has improved in recent years through studies of bronchoalveolar lavage cells and fluid, the genetic predisposition and trigger factors (and their interrelationship) remain unclear. Previous reports of familial clustering and varying prevalence of sarcoidosis in different populations suggested molecular epidemiological heterogeneity. This review focuses specifically on two pivotal areas that have been the subjects of intensive investigation recently: a) triggering by infective agents and b) host genetic susceptibility and relates these to broader issues of pathogenesis. It is concluded that one or more microbes behaving in a non-infectious fashion in a genetically predisposed individual trigger the sarcoidosis granulomatous response.

Ace gene I/D polymorphism and sarcoidosis pulmonary disease severity.

Previous studies of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in sarcoidosis have revealed both ethnic heterogeneity of I/D frequencies and controversy surrounding the association between the polymorphism and severity of disease. The objective of this study was, therefore, to clarify the role of the ACE I/D polymorphism in (1) disease susceptibility, (2) pulmonary disease severity (with particular reference to pulmonary fibrosis), and (3) pulmonary disease progression, in two distinct European sarcoidosis populations. Standard chest radiographic staging was performed on 118 UK and 56 Czech white patients with sarcoidosis at 2 yr from presentation. Pulmonary function data were analyzed, and patients were then categorized according to disease severity. A PCR-SSP assay was used to determine the ACE I/D genotype of each patient studied. The I/D allele frequencies from these patients were compared with frequencies from ethnically matched UK (n = 386) and Czech (n = 179) control subjects using a chi-square contingency table. No significant differences were seen in the distribution of the ACE I/D genotypes, allele frequencies or phenotype frequencies. Furthermore, no association was found between the ACE I/D polymorphism and pulmonary disease severity, fibrosis, and progression. We conclude that the ACE I/D polymorphism has no role in sarcoidosis susceptibility in European whites and that it is not a regulatory variant in this disease.

Class II HLA associations with autoantibodies in scleroderma: a highly significant role for HLA-DP.

Scleroderma is a condition of variable phenotype characterised by fibrosis of the skin and internal organs. There is a range of disease-specific autoantibodies found in the sera of patients. The aims of this study were to: (1) investigate the role of the MHC and particularly HLA-DP in the production of autoantibodies; (2) investigate clinical associations with autoantibodies. We have performed HLA class II typing using PCR with sequence-specific primers on DNA samples from 202 scleroderma patients and 307 UK control subjects. All patients had well defined clinical phenotypes. Sera from patients were examined for the presence of disease specific autoantibodies in particular the anti-topoisomerase autoantibody (ATA), the anti-centromere autoantibody (ACA) and the anti-RNA polymerase autoantibody (ARA). There was a striking association between HLA-DPB1*1301 and ATA (Pcorr = 0.0001). In addition, ATA was associated with HLA-DRB1*11 and the anticentromere autoantibody (ACA) with HLA-DRB1*04, HLA-DRB1*08 (P = 0.001) and HLA-DQB1 alleles with a glycine residue at position 26. Very strong associations were detected between clinical phenotypes and autoantibodies. ATA was associated with pulmonary fibrosis (P = 0.00002), anti-RNA polymerase autoantibody (ARA) with renal involvement (P = 0.0000006) and diffuse skin disease (P = 0.00001), and ACA with limited skin involvement (P = 0.00002) and protection against pulmonary fibrosis (P = 0.0000003). We have identified a significant association between the ATA and HLA-DPB1*1301 which may provide an insight into how this autoantibody is formed. Patient clinical characteristics depend on the autoantibodies they carry.

Mannose-binding lectin promoter and structural gene variants in sarcoidosis.

BACKGROUND: Sarcoidosis is a chronic granulomatous disease of unknown aetiology. Studies have suggested that the causative agent may be an infectious micro-organism. The mannose binding lectin (MBL) is involved in innate immunity to a wide range of micro-organisms. Mutations in the promoter region and exon 1 of the MBL gene occur with high frequency and are associated with reduced serum levels of MBL and increased susceptibility to microbial diseases. This study investigated whether MBL variants predispose to sarcoidosis by increasing their susceptibility to micro-organisms. METHODS: MBL gene promoter and exon 1 variants were detected by sequence specific primer polymerase chain reaction (SSP-PCR) in 167 UK Caucasian sarcoidosis patients and 164 control subjects. Severity of pulmonary disease outcome among patients was assessed by radiography after a minimum of 4 years from disease onset and classified as mild, moderate, and severe disease categories, accordingly. RESULTS: MBL variant frequencies were similar in patients and controls studied. Among sarcoidosis patients, the frequencies of variants were similar regardless of severity of disease outcome. The average patient ages at time of diagnosis were similar for all MBL genotypes. CONCLUSIONS: MBL gene variants do not appear to influence susceptibility to sarcoidosis, age of disease onset, or severity of disease.

Analysis of MHC encoded antigen-processing genes TAP1 and TAP2 polymorphisms in sarcoidosis.

Sarcoidosis is a chronic granulomatous disease of unknown etiology. Several studies have suggested involvement of human leukocyte antigen (HLA) genes in sarcoidosis susceptibility. HLA associations described have not been consistent, possibly because of additional susceptibility genes adjacent to or within the major histocompatibility complex (MHC) such as genes for the transporter associated with antigen processing (TAP). The aim of this study was to analyze TAP gene polymorphisms in patients with sarcoidosis using the amplificatory refraction mutation system (ARMS) PCR. To determine whether any association between TAP gene variation and sarcoidosis was ethnic-independent we examined two European populations: 117 unrelated UK Caucasoid patients with sarcoidosis and 290 healthy UK control subjects, and 87 unrelated Polish Slavonic patients with sarcoidosis and 158 healthy Polish control subjects. We detected significant differences in TAP2 between the UK control and patient groups, and in TAP2 between the Polish control and patient groups. Comparing the UK and Polish control groups, we observed a difference in TAP1. Examination of HLA-DPB1 in our UK population showed no associations with disease or between variants at the TAP gene loci and HLA-DPB1 variants. These results suggest associations at the TAP loci occur independently of HLA-DPB1 associations, that TAP associations seen may be involved in determining sarcoidosis susceptibility, and that such susceptibilities differ between UK and Polish populations. This first study of TAP genes in UK and Polish sarcoid populations has demonstrated the importance of using multiple defined ethnic populations in defining the role genetic factors play in sarcoidosis susceptibility and the importance of candidate gene studies.

Polymorphic analysis of the high-affinity tumor necrosis factor receptor 2.

The tumor necrosis factor receptor 2 (TNF-RII, CD120b, TNF-R p75/80) gene has recently been characterised. It is located on chromosome 1p362 and consists of 10 exons and 9 introns A number of biallelic polymorphisms have been found in exons 4, 6, 9 and 10 based on differences between published sequences. In this study we have used polymerase chain reaction methodology in association with sequence-specific primers (PCR-SSP) incorporating mismatches at the 3' end to identify these polymorphisms. We were able to confirm the presence of a single biallelic polymorphism in exon 6 corresponding to a (T/G) at nucleotide 676 of TNF-RII mRNA (gb:M32315) which results in an amino acid change and three biallelic polymorphisms in exon 10 (in the3'UTR) corresponding to (A/G) at nucleotide 1663, (T/G) at nucleotide 1668 and a (C/T) at nucleotide 1690 of gb:M32315, whereas no polymorphisms were observed in exons 4 and 9. Here we report that in 192 unrelated UK Caucasian individuals the allele frequencies determined by direct counting were: 676-T (0.77), 1663-G (0.51), 1668-T (0.95), and 1690-T (0.64) and the calculated gene frequencies were; 676-T (0.52), 676-G (0.12); 1663-G (0.30), 1663-A (0.28); 1668-T (0.77), 1668-G (0.025); and 1690-T (0.40), 1690-C (0.20). Furthermore, the presence of an A allele at nucleotide position 1663 was found to be strongly associated with the presence of a C allele at nucleotide position 1690 and a G allele at nucleotide position 1668 whereas the presence of a G allele at position 1663 was associated with the absence of a C allele at nucleotide position 1690.

Psoralen photochemotherapy, clinical efficacy, and photomutagenicity: the role of molecular epidemiology in minimizing risks.

Photochemotherapy employing 8-methoxypsoralen and ultraviolet radiation (PUVA) is widely used in the treatment of psoriasis. The photoactivation of psoralens in skin cells leads to DNA photoadduct formation which may be responsible for the efficacy of PUVA. Subsequent mutations may lead to the increased incidence of squamous cell carcinoma (SCC). Mutations in the p53 tumor suppressor gene have been detected in many human cancers. In this review, p53 mutation spectra in murine and human SCC are compared to those obtained from murine cells and skin treated with PUVA as well as to the p53 mutation spectrum in human solar SCC. While the expected psoralen-type mutations at alternating AT sites were detected in the treated cells and murine SCC (average frequency > 40%), such mutations were not commonly detected in the human SCC (< 10%). Other common mutations in the human SCC included: CG-->TA transitions (18%) and CG-->AT and TA-->GC transversions (17 and 25%, respectively). In addition, the frequency of UVB-type mutations at dipyrimidine sites (CC-->TT) in the SCC PUVA-treated psoriasis patients was comparable to that in patients with SCC from only solar exposure. A review of therapeutic history of these patients showed that many had also received UVB phototherapy. Furthermore, because sunlight is thought to be beneficial for psoriasis, nontherapeutic, casual UVB exposure cannot be excluded. Thus, the PUVA SCC may have arisen from the solar mutations and PUVA may enhance tumor progression by other epigenetic effects.

Is the world paying enough attention to the AIDS epidemic in Ukraine and other Newly Independent States?

PIP: HIV infection rates in Russia and Ukraine have reached levels which confirm that the two countries are currently experiencing an HIV/AIDS epidemic. Other countries of the former Soviet Union have seriously high infection rates. For example, in 1997, the UN estimated that there were 100,000 new HIV infections in Eastern Europe. According to Ukraine government HIV testing figures, from 1987 through 1994, only 398 of more than 39 million HIV tests yielded positive results. However, in 1995, 1499 of 3,515,197 tests performed were seropositive. Of 2,867,049 tests performed in 1996, 11,150 were HIV-seropositive. 5244 IV drug users and 1887 prisoners were among those who tested positive in 1996. Of 255,122 STD patients tested in 1996, 3.7% were HIV-positive, with rates highest in the Mykolayiv region (22.7%), Odessa (13.3%), and Kiev (5.8%). Urgent measures need to be taken to check the spread of HIV in the Newly Independent States. In describing AIDS and STDs in the region, the author draws from UN statistics, news stories, the government of Ukraine, and his personal experience developing a social marketing project in Odessa, Ukraine. He also notes the efforts of the Futures Group in Odessa.^ieng

Massive blood loss during tonsillectomy in a child with congenital venous malformation.

Tonsillectomy and adenoidectomy have become frequently performed outpatient procedures and are generally considered to have a low morbidity profile. Postoperative haemorrhage remains a rare but important complication, while intraoperative uncontrollable bleeding is extremely uncommon. A child with congenital vascular malformation of the lip and oropharynx undergoing tonsillectomy experienced massive blood loss, subsequent resuscitation and significant perioperative morbidity including a prolonged intensive care unit stay. Preoperative/preanaesthetic nasopharyngoscopic exam and magnetic resonance imaging did not reveal vascular prominence of the tonsils. Preoperative consideration of angiography or magnetic resonance angiography may be prudent to avoid this potentially fatal complication.

Motor unit control properties in constant-force isometric contractions.

1. The purpose of this study was 1) to characterize the decrease observed in mean firing rates of motor units in the first 8-15 s of isometric constant-force contractions and 2) to investigate possible mechanisms that could account for the ability to maintain force output in the presence of decreasing motor unit firing rates. 2. The decrease in mean firing rates was characterized by investigating myoelectric signals detected with a specialized quadrifilar needle electrode from the first dorsal interosseus (FDI) and the tibialis anterior (TA) muscles of 19 healthy subjects during a total of 85 constant-force isometric contractions at 30, 50, or 80% of maximal effort. The firing times of motor units were obtained from the myoelectric signals with the use of computer algorithms to decompose the signal into the constituent motor unit action potentials. Time-varying mean firing rates and recruitment thresholds were also calculated. 3. Motor units detected from the TA muscle were found to have a continual decrease in their mean firing rates in 36 of 44 trials performed during isometric ankle dorsiflexion at force values ranging from 30 to 80% of maximal effort and a duration of 8-15 s. Likewise, motor units detected in the FDI muscle displayed a decrease in firing rate in 32 of 41 trials performed during constant-force isometric index finger abduction for contractions ranging from 30 to 80% of maximal effort. In 14 contractions (16% of total), firing rates were essentially constant, whereas in 3 contractions (4%), firing rates appeared to increase. 4. Motor units with the higher recruitment thresholds and lower firing rates tended to display the greater decreases in firing rate over the constant-force interval, whereas motor units with lower recruitment thresholds and higher firing rates had lesser rates of decrease. Furthermore, increasing contraction levels tended to intensify the decrease in the motor unit firing rates. 5. Three possible mechanisms were considered as factors responsible for the maintaining of force output while motor units decreased their firing rates: motor unit recruitment, agonist/antagonist interaction, and twitch potentiation. Of these, motor unit recruitment was discarded first because none was observed during the 8-15 s duration of any of the 85 contractions. Furthermore, contractions outside the physiological range of motor unit recruitment (at 80% of maximal effort) revealed the same decreasing trend in firing rates, ruling out recruitment as the means of sustaining force output. 6. The role of agonist or antagonist muscle interaction was investigated with the use of the muscles controlling the wrist joint. Myoelectric signals were recorded with quadrifilar needle electrodes from the wrist extensor muscles while myoelectric activity in the wrist flexor muscles was concurrently monitored with surface electrodes during constant-force isometric wrist extension at 50% of maximal effort. Firing rates of the motor units in the wrist extensor muscles simultaneously decreased while the flexor muscles were determined to be inactive. 7. All the findings of this study regarding the behavior of the firing rates could be well explained by the reported characteristics of twitch potentiation that have been previously documented in animals and humans. 8. The results of this study, combined with the results of other investigators, provide the following scenario to explain how a constant-force isometric contraction is sustained. As the contraction progresses, the twitch force of the muscle fibers undergoes a potentiation followed by a decrease. Simultaneously, the "late adaptation" property of the motoneuron decreases the firing rate of the motor unit. Findings of this study suggest that voluntary reduction in firing rates also cannot be ruled out as a means to augment the adaptation in motoneurons. (ABSTRACT TRUNCATED)

Demographic Health Survey: Xay Thani district of Vientiane prefecture, Lao People's Democratic Republic.

PIP: This article describes a demographic and health survey of 1608 married women of reproductive age, 15-44 years, from a sample of 30 villages in Xay Thani within 30-60 km of Vientiene, Lao People's Democratic Republic. It is expected that the social, economic and health conditions would be higher given the proximity to the capital city with bus service and paved roads. The physician to patient ratio is 1/1400 persons compared to rest of the country at 1/12,600. The physical conditions in the 60% farming community show that 85% are without motor transport and 40% without electricity. The mean age of respondent was 29 years. 81% could read a newspaper and 19% had no formal education and were unable to read. 87% of those 35-39 years and 48% of those 40-44 years had no formal education. The UN estimated Laotian female literacy to be 35% in 1989. It is possible the higher literacy is due to radio, television, and newspaper accessibility. 55% owned radios and 25% had televisions. 85% accepted the idea of family planning messages on television. The mean number of living children ranged from a high of 6.86 for those 40-44 to low of 1.09 for those 19 and 2.0 for those 20-24. The average was 3.82. Corresponding mean live births were 7.91 and 1.25 and 2.25. The infant mortality rate can not be determined from the data but is expected to be high. Knowledge of reproductive fertility and contraceptives was low. 86% were unaware of the timing of ovulation for most ages. 25% were aware of IUDs, condoms, tubectomy, vasectomy, periodic abstinence, or withdrawal, and 35% were aware of pills. Only 16% knew where to obtain contraceptives. The contraceptive prevalence rate (CPR) was 17.6% for modern methods. 17% were pregnant and 3% were unsure. Only 3.6% of those 19 have used any method and 1.8 a modern method. The CPR for 20-24 years old was 12.1% and increased with age. 70% of those 30 years did not want to be pregnant. Desired number of children was 3 or more, and mean desired was 5. A high infant mortality rate may account for the higher number of desired children. Reducing infant mortality and delaying age at 1st pregnancy would positively affect maternal and child health, as would sanitation improvements. 58% reported no toilet facilities. 35% reported that their youngest child had not received immunization. A comprehensive family planning program is recommended.^ieng

Physiological responses to different roller skiing techniques.

This study compared the physiological responses during roller skiing with the V1 skate, kick double pole, and double pole techniques. Eight male nordic ski racers roller skied over a flat one-mile track at 14 and 18 km.h-1 using each of the three techniques under study. Heart rates and oxygen uptakes were measured during the last minute of each bout, ratings of perceived exertion were requested immediately after each bout, and capillary blood lactate concentrations were determined 3 min after each bout. The double pole technique was found to be significantly more economical (P less than 0.05) than the other techniques, as demonstrated by a 12% lower oxygen consumption. No differences were found between the V1 skate and the kick double pole techniques for any of the variables studied. The findings of similar physiological responses with the V1 skate and kick double pole techniques suggest that these techniques should induce similar cardiovascular adaptations when roller skiing at the same speed on flat terrain.

Effect of adrenal function on gastrointestinal peptide release in experimental cardiac arrest.

Pancreatic polypeptide (PP), neurotensin, substance P, and vasoactive intestinal polypeptide (VIP) are peptides that modify various autonomic and neural functions. These substances are secreted into the blood in response to physiologic stimuli affecting the gastrointestinal tract. To determine the effect of adrenal hormones on gastrointestinal peptide release we measured blood levels of PP, VIP, substance P, and neurotensin in adrenalectomized and intact dogs undergoing cardiac arrest and cardiopulmonary resuscitation (CPR), a condition associated with maximal adrenal stimulation. One hour after completion of abdominal surgery consisting of bilateral adrenalectomy or exposure of the adrenal glands (sham operation), ventricular fibrillation was induced in 19 dogs by direct ventricular discharge. Despite marked elevations of plasma epinephrine and norepinephrine, CPR was associated with minimal endocrine gastrointestinal involvement, restricted to increased VIP levels in sham-operated dogs. No specific gastrointestinal peptide response to cardiac arrest was seen in adrenalectomized animals, but their plasma PP and VIP levels were higher than those of sham-operated dogs. Therefore, acute maximal adrenal stimulation is associated with selective VIP release. In addition, the higher level of the vagally controlled plasma PP in adrenalectomized animals suggests a tonic inhibitory effect of adrenal secretions on the release of this peptide.

Plasma catecholamine and serum cortisol responses to experimental cardiac arrest in dogs.

The plasma catecholamine and serum cortisol responses to cardiac arrest (ventricular fibrillation), cardiopulmonary resuscitation (CPR), and ventricular defibrillation were examined in 10 intact (sham-operated controls) and 10 bilaterally adrenalectomized dogs. One hour after surgery, the cardiac ventricles were electrically fibrillated, and 30 s later Standard American Heart Association CPR was begun. After 12 min of CPR, the ventricles were defibrillated. Cardiac arrest per se results in a massive increase in plasma epinephrine and norepinephrine concentrations and indicates that the adrenal medullas are the predominant source of this response. Although the epinephrine response was virtually nonexistent in the adrenalectomized dogs, the norepinephrine response was approximately 30% of that in the sham-operated control animals. Thus there is an adrenomedullary, and perhaps a sympathetic neural, component to the sympathochromaffin response to cardiac arrest. Resuscitation from experimental cardiac arrest tended (P greater than 0.05 less than 0.1) to be lower in the adrenalectomized dogs (1 of 10) than in the animals with intact adrenal glands (6 of 10).

Effects of naloxone on the adrenomedullary response during and after cardiopulmonary resuscitation in dogs.

To determine the effects of naloxone, an opiate antagonist, on the adrenomedullary response to cardiac arrest, plasma epinephrine and norepinephrine levels were measured before, during, and after cardiac arrest in dogs. Ventricular fibrillation was induced in 12 dogs anesthetized with pentobarital sodium (30 mg/kg) and standard American Heart Association cardiopulmonary resuscitation (CPR) was begun using a mechanical device. At 6.5 minutes of CPR, naloxone (10 mg/kg) or 0.9% saline (10 ml) was given intravenously. At 12 minutes of CPR, the cardiac ventricles were electrically defibrillated. Plasma epinephrine and norepinephrine levels were measured before ventricular fibrillation; at 2.5, 4.5, 9.5, and 11.5, minutes of CPR; and at 5, 10, 15, and 20 minutes after resuscitation. Epinephrine and norepinephrine increased from prearrest levels of 3.66 +/- 0.67 (+/- SE) and 24.02 +/- 3.67 ng/ml to 66.67 +/- 9.65 and 74.00 +/- 9.91 ng/ml, respectively, at 4.5 minutes of CPR. After resuscitation, norepinephrine levels remained slightly elevated, while epinephrine fell to prearrest levels. Naloxone did not cause a significant change in either epinephrine or norepinephrine from 6.5 minutes of CPR (time of treatment) through 20 minutes postresuscitation. In addition, naloxone had no effect on either the end-diastolic pressure difference during CPR or resuscitation outcome. We conclude that cardiac arrest causes significant increases in plasma epinephrine and norepinephrine levels, which remain elevated for the duration of the arrest, and that naloxone has no effect on these levels.

Cerebrospinal fluid changes in experimental cardiac arrest (maximal stress).

Cardiac arrest produces a prompt and maximal increase of plasma catecholamines, with associated elevations of the hormones involved in the endocrine response to stress. To investigate the participation of the central nervous system (CNS) in the generation of the endocrine response, the catecholamines epinephrine and norepinephrine in cerebrospinal fluid (CSF) were measured before, during, and after cardiac arrest accompanied by cardiopulmonary resuscitation (CPR) in adrenalectomized (ADX) and sham-operated (SHAM) dogs. We also determined the activity of acetylcholine esterase (AChE), an intracellular enzyme released into the CSF after hypothalamic or caudate stimulation. During CPR, plasma epinephrine increased significantly in SHAM but not ADX dogs, increasing from (mean +/- SE) 480 +/- 171 to 29,800 +/- 14,200 pg/ml (P less than 0.05). Prearrest CSF norepinephrine was higher in ADX than SHAM dogs and increased in both groups with cardiac arrest, but the increase was significant only in SHAM animals; CSF epinephrine remained unchanged during or after cardiac arrest. CSF AChE activity increased during and after defibrillation; the difference with basal levels became significant when the peak postarrest values were considered (P less than 0.05). These results document biochemical changes occurring in the CNS during maximal stress represented by cardiac arrest. It is suggested that CSF norepinephrine and AChE activity elevations are markers for hypothalamic activation from the stress of cardiac arrest.

Effects of cell size and exercise on glucose uptake and metabolism in adipocytes of female rats.

The purpose of this study was to attain a better understanding of how the adipocyte transports and metabolizes glucose with and without the influence of exercise training. Rates of 2-deoxyglucose and glucose oxidation, using [1-14C]-and [6-14C]glucose, were measured in adipocytes from exercise-trained and sedentary control female rats of the same age. The trained animals were exercised by swimming, 6 h/day, 5 days/wk for 10 wk. The fat cells of the sedentary rats were significantly larger (P less than 0.005) than the trained animals and had very low rates of glucose uptake and [1-14C]- and [6-14C]glucose oxidation. The adipocytes of the trained rats were very responsive to insulin with 2-deoxyglucose rates seven times higher than those of the control animals and [1-14C]- and [6-14C]-glucose oxidation rates 14- and 13-fold (respectively) larger than control values. Comparisons of the data from exercised animals to younger sedentary rats indicates that glucose oxidation remains normal in the adipocytes of the trained animals whereas glucose transport is greatly improved. If the older sedentary controls are compared to younger animals, it can be seen that as the cell enlarges it loses its ability to take up or metabolize glucose. The combination of a loss in glucose transporting capacity with cellular enlargement and an increase in glucose uptake with exercise training suggests that movement of glucose across the cell membrane may be a limiting factor in glucose utilization in fat cells.