Contribution of surgical specialization to improved colorectal cancer survival.

BACKGROUND: Reorganization of colorectal cancer services has led to surgery being increasingly, but not exclusively, delivered by specialist surgeons. Outcomes from colorectal cancer surgery have improved, but the exact determinants remain unclear. This study explored the determinants of outcome after colorectal cancer surgery over time. METHODS: Postoperative mortality (within 30 days of surgery) and 5-year relative survival rates for patients in the West of Scotland undergoing surgery for colorectal cancer between 1991 and 1994 were compared with rates for those having surgery between 2001 and 2004. RESULTS: The 1823 patients who had surgery in 2001-2004 were more likely to have had stage I or III tumours, and to have undergone surgery with curative intent than the 1715 patients operated on in 1991-1994. The proportion of patients presenting electively who received surgery by a specialist surgeon increased over time (from 14·9 to 72·8 per cent; P < 0·001). Postoperative mortality increased among patients treated by non-specialists over time (from 7·4 to 10·3 per cent; P = 0·026). Non-specialist surgery was associated with an increased risk of postoperative death (adjusted odds ratio 1·72, 95 per cent confidence interval (c.i.) 1·17 to 2·55; P = 0·006) compared with specialist surgery. The 5-year relative survival rate increased over time and was higher among those treated by specialist compared with non-specialist surgeons (62·1 versus 53·0 per cent; P < 0·001). Compared with the earlier period, the adjusted relative excess risk ratio for the later period was 0·69 (95 per cent c.i. 0·61 to 0·79; P < 0·001). Increased surgical specialization accounted for 18·9 per cent of the observed survival improvement. CONCLUSION: Increased surgical specialization contributed significantly to the observed improvement in longer-term survival following colorectal cancer surgery.

Quality of care in rectal cancer surgery. Exploring influencing factors in the West of Scotland.

AIM: To assess variability in the proportions of types of major resection for rectal cancer throughout the west of Scotland (WoS) and ascertain factors explaining the variability. METHOD: Retrospective cohort study of a regional population clinical audit database. This was linked to cancer registrations and death certificates in order that outcome analyses could be derived. Univariate and multivariate binary logistic regression analyses were used to explore determinants of survival. RESULTS: A total of 1574 patients met the inclusion criteria. The age range was from 22 to 97 years. The mean age was 67, median age 68 and the standard deviation was 11.5. The majority of patients (61%) were male. Unlike previous series, male patients and those with poorer socioeconomic circumstances (SEC) were no more likely to receive an abdominoperineal excision (APE) procedure for rectal cancer. CONCLUSION: Variation exists in the west of Scotland regarding surgical treatment for rectal cancer. We found no difference in the type of procedure offered according to sex, intent of operation or socioeconomic circumstances with reference to APE and anterior resection (AR) for rectal cancer. We conclude therefore that our region provides an equitable service on grounds of sex and SEC. This demonstrates that an equitable surgical service has been provided for those suffering from rectal cancer. Circumferential margin positivity was four times more likely in an APE than an AR for rectal cancer. This is not explained by age, stage, sex, socioeconomic circumstances (SEC), volume of surgery, intent of operation, type of admission or year of incidence.

Mechanical bowel preparation does not influence outcomes following colonic cancer resection.

BACKGROUND: Meta-analyses have indicated that preoperative mechanical bowel preparation (MBP) confers no clear benefit and may indeed be harmful for patients with colorectal cancer. The effects of bowel preparation on longer-term outcomes have not been reported. The aim was to compare long-term survival and surgical complications in patients who did or did not receive MBP before surgery for colonic cancer. METHODS: This was a retrospective cohort study of all patients undergoing potentially curative surgery for colonic cancer after routine hospital admission in the West of Scotland between January 2000 and December 2005. Clinical audit data were linked to cancer registrations and death certificates. Kaplan-Meier and Cox proportional hazards models were used to explore determinants of survival. RESULTS: A total of 1730 patients underwent potentially curative surgery for colonic cancer, of whom 886 (51·2 per cent) were men. The mean(s.d.) age was 69·7(10·6) years. Some 1460 patients (84·4 per cent) received MBP. Median follow-up was 3·5 (range 0·1-6·7) years. There were no statistically significant differences in 30-day postoperative complication rates between groups. The unadjusted hazard ratio (HR) for death from all causes for patients treated with MBP (versus no MBP) was 0·72 (95 per cent confidence interval 0·57 to 0·91). Multivariable analysis with adjustment for age, sex, socioeconomic circumstances, disease stage and presentation for surgery showed that MBP had no independent effect on all-cause mortality (HR 0·85, 0·67 to 1·10). CONCLUSION: Neither postoperative complications nor long-term survival are improved by MBP before colonic cancer surgery.

C-reactive protein as a predictor of postoperative infective complications following elective colorectal resection.

AIM: C-reactive protein (CRP) may be useful in predicting postoperative complications [1]. We investigated the sensitivity and specificity of postoperative CRP for infective complications after elective colorectal surgery. METHOD: One hundred and sixty consecutive patients (72 years old; interquartile range, 63-79) undergoing elective resection for colorectal cancer treated between September 2003 and October 2006 were studied. Details of the postoperative course were prospectively entered into a database. Of the 160 patients, 10 had incomplete CRP data and were excluded from further analysis. RESULTS: Infective complications occurred in 21%, with an overall complication rate of 29%. Infective complications occurred as follows: respiratory (10), wound (9), urinary tract (2) and central line infection (1), anastomotic leakage (5), intra-abdominal abscess (3) and septicaemia of unknown origin (2). There were three postoperative deaths. The positive predictive value for infection of CRP > 145 mg/l on postoperative day 4 was 61%. The negative predictive value of CRP < 145 mg/l on postoperative day 4 for an infective complication was 96%. CONCLUSION: A CRP > 145 mg/l on day 4 has high specificity and sensitivity for infective complications following elective colorectal resection.

Perineum compression during EAUS enhances visualization of anterior anal sphincter defects.

OBJECTIVE: Endo-anal ultrasound (EAUS) can detect anal sphincter injuries. However, anterior external anal sphincter (EAS) defects can be difficult to define. We assessed different EAUS techniques to determine if any particular method improved defect identification. METHOD: Ninety females with faecal incontinence were prospectively studied. Wexner faecal incontinence scores were obtained. All patients underwent anorectal manometry and EAUS using three different techniques: standard, digit-assisted (gloved finger pressing on posterior vaginal wall) and balloon-assisted (standard balloon inflated into the vagina). The three techniques were assessed by comparing defect characteristics (detection, angle, edges and scar tissue), and perineal body thickness. All measurements were performed at the mid anal canal level. RESULTS: are expressed as medians (IQR). Results Standard EAUS (S-EAUS) identified a sphincter defect in 54 patients. Digit assisted EAUS (D-EAUS) and balloon-assisted EAUS (B-EAUS) ultrasound revealed a sphincter defect in additional 11 and 9 patients respectively compared to S-EAUS. Correlation of maximum squeeze pressure with EAUS findings improved on D-EAUS and B-EAUS. The defect angle was significantly wider with D-EAUS and B-EAUS [S-EAUS 90 degrees (63-97), D-EAUS 100 degrees (81-101.5), B-EAUS 100 degrees (80-105), P = 0.0005]. The perineal body was significantly thicker when measured with B-EAUS [D-EAUS 9 mm (7-10) vs B-EAUS 10 mm (8-11), P = 0.0005]. Inter-observer agreement was comparable [S-EAUS (K) = 0.677, D-EAUS (K) = 0.658, B-EAUS (K) = 0.601]. CONCLUSION: EAS anterior defect detection and definition on EAUS may be improved by the demarcation and gentle pressure on the posterior vaginal wall.

The jellyfish green fluorescent protein: a new tool for studying ion channel expression and function.

Two methods are described for using the jellyfish green fluorescent protein (GFP) as a reporter gene for ion channel expression. GFP fluorescence can be used to identify the transfected cells, and to estimate the relative levels of ion channel expression, in cotransfection experiments. A GFP-NMDAR1 chimera can be constructed that produces a functional, fluorescent receptor subunit. These methods should facilitate studies of ion channel expression, localization, and processing.

Nicorandil-induced colonic ulceration: a new cause of colonic ulceration. Report of four cases.

PURPOSE: Nicorandil is a widely used third-line treatment for ischemic heart disease. It can be associated with the development of stomatitis and oro-anal ulceration. The current report suggests an association between nicorandil and the development of colonic ulceration, both in isolation and in combination with anal ulceration. METHODS: This is a case report of four patients with new onset lower gastrointestinal symptoms. All had a history of ischemic heart disease and angina. All were taking several cardiac medications, including nicorandil. RESULTS: Four patients (3 men) were investigated. Colonoscopy revealed both solitary and multiple colonic ulcers. Pathology showed acute nonspecific inflammation. Two patients also displayed concomitant anal ulceration. Nicorandil therapy was stopped in all patients. No other active treatment was offered. All patients became asymptomatic within six weeks of cessation of nicorandil therapy with resolution of the anal and colonic ulceration. CONCLUSION: Nicorandil may induce colonic ulceration and should be considered in the differential diagnosis of idiopathic colonic ulceration in appropriate patients.

Anterior anal fissures are associated with occult sphincter injury and abnormal sphincter function.

OBJECTIVE: The pathogenesis of chronic anal fissure (CAF) remains incompletely understood but most are associated with a high resting anal pressure and reduced perfusion at the fissure site. To date, no major distinction has been made between anterior and posterior anal fissures and their aetiology and treatment. We compared anterior and posterior fissures in patients who have failed to respond to medical treatment with respect to their underlying aetiology, anal canal pressures and sphincter muscle integrity. METHOD: Seventy consecutive patients (54 female:16 male) with a symptomatic CAF and 39 normal controls (19 female:20 male) without evidence of significant ano-rectal pathology were prospectively assessed by manometry and anal endosonography. RESULTS: Anterior anal fissures were identified in a younger age group [33 years (IQR 26-37) vs 41 years (IQR 36-52)] and predominantly in women. Anterior fissure patients were significantly more likely to have underlying external anal sphincter defects compared with posterior fissures [OR 10.9 (95% CI 3.4-35.4)]. Maximum resting pressure was not significantly elevated for anterior fissures compared with controls (P = 0.316) but was significantly elevated in posterior fissures (P = 0.005). The maximum squeeze pressure was significantly lower in the anterior fissure group [167 cmH2O (IQR 126-196) vs 205 cmH2O (IQR 174-262), P = 0.004]. A history of obstetric trauma was significantly associated with anterior fissure location [OR 13.9 (95% CI 3.4-55.7)]. CONCLUSIONS: Anterior anal fissures are associated with occult external anal sphincter injury and impaired external anal sphincter function compared with posterior fissures. These findings have implications for treatment, especially if a definitive procedure, such as lateral internal sphincterotomy, is considered.

Correlation between anal manometry and endosonography in females with faecal incontinence.

OBJECTIVE: Female faecal incontinence (FI) is largely because of sphincter injury at childbirth. Sphincter assessment aims to identify surgically correctable defects. We aimed to identify endoanal ultrasonography (EAUS) parameters that correlate with sphincter function. METHOD: One hundred females with FI and 28 healthy asymptomatic females were prospectively assessed. Wexner FI score was recorded and all subjects underwent anorectal manometry and EAUS. Multiple EAUS parameters were assessed and correlated with external (EAS) and internal (IAS) anal sphincter function, determined by maximum squeeze pressure (MSP) and maximum resting pressure (MRP) respectively. Parameters included sphincter quality (echogenicity), thickness, perineal body thickness (PBT) and defect characteristics (angle, length). Results are expressed as medians and interquartile range (IQR). RESULTS: Median Wexner score was 14 (12-17). Maximum EAS thickness significantly correlated with MSP (P = 0.019). EAS defects were detected in 84 patients and seven controls (P < 0.0001). Full-length EAS defects were only detected in FI group and had significantly lower MSP [MSP mmHg: full length 85 (65-103) vs partial length 119 (75-155), P = 0.006]. FI patients were more likely to have a mixed echogenicity of EAS compared with controls. EAS ring quality, PBT and defect angle were not significant. IAS quality was significantly associated with MRP [MRP mmHg: uniform 62 (43-82) vs mixed 47 (30.5-57.5), P = 0.002]. CONCLUSION: Certain EAUS parameters can be predictive of anal sphincter function. These include the presence of an EAS defect and its length, EAS maximum thickness, IAS ring quality. Integration of these parameters can give better EAUS correlation with manometry for FI evaluation.

A computer model of the position of the combined component in the prevention of impingement in total hip replacement.

Dislocation remains a major concern after total hip replacement, and is often attributed to malposition of the components. The optimum position for placement of the components remains uncertain. We have attempted to identify a relatively safe zone in which movement of the hip will occur without impingement, even if one component is positioned incorrectly. A three-dimensional computer model was designed to simulate impingement and used to examine 125 combinations of positioning of the components in order to allow maximum movement without impingement. Increase in acetabular and/or femoral anteversion allowed greater internal rotation before impingement occurred, but decreases the amount of external rotation. A decrease in abduction of the acetabular components increased internal rotation while decreasing external rotation. Although some correction for malposition was allowable on the opposite side of the joint, extreme degrees could not be corrected because of bony impingement. We introduce the concept of combined component position, in which anteversion and abduction of the acetabular component, along with femoral anteversion, are all defined as critical elements for stability.

Recognition and treatment of adult respiratroy distress syndrome secondary to viral interstitial pneumonia.

Four cases of adult respiratory distress syndrome secondary to viral interstital pneumonia were treated successfully. The illnesses started with a prodrome of upper respiratory symptoms. The development of dyspnea was a key symptom from which point respiratory failure developed within 24 to 48 hours. Chest roentgenograms showed alveolar infiltrative patterns which later became coalescent. The clinical course consisted of fever, dyspnea, hypoxia and acidosis, There was no response to therapy with antibiotics, 100 per cent oxygen by mask and intermittent positive pressure breathing (IPPB) over the first 24 hours. Supportive therapy then initiated included endotracheal intubation, the administration of humidified oxygen by volume cycled respirator with positive end expiratory pressures of 10 to 15 cm H2O and corticosteroids. It is concluded that early recognition of the syndrome, coupled with prompt insituition of aggressive supportive respiratory management may be lifesaving in patints with severe interstitial pneumonia.

The humoral immune response after thermal injury: an experimental model.

BACKGROUND: Severe thermal injury is associated with major alterations in cell-mediated immunity. Because most B-cell responses are regulated or critically dependent on T-cell help, it is not surprising that many studies have also shown a variety of defects in humoral immunity after thermal injury. However, the nature of the relationship between the in vitro ability to produce antibody and subsequent in vivo responses remains unclear. METHODS: With a murine model of thermal injury, the primary and secondary humoral immune response to tetanus toxoid (TT) was examined during a 6-week period after sham burn or burn injury. Serum anti-TT titers and the numbers of anti-TT-secreting splenocytes were determined. RESULTS: Splenocytes from burned animals displayed normal or decreased TT-specific immunoglobulin (Ig) M plaque formation. In contrast, however, IgG plaque formation was persistently increased for up to 6 weeks after thermal injury, suggesting a switch from IgM to IgG antibody production. Conversely serum titers of TT-specific IgG antibody were persistently lower in burn, compared with sham groups. Changes in serum immunoglobulin levels did not account for this marked discrepancy between enhanced in vitro IgG plaque formation but impaired in vivo levels of TT antibody. CONCLUSIONS: The data suggest that thermal injury is associated with a diminished ability to propagate and maintain a normal IgG antibody response, despite the presence of normal or increased numbers of antigen-specific B cells.

Molecular mechanisms of decreased interleukin-2 production after thermal injury.

BACKGROUND: Among the fundamental immunologic abnormalities induced by serious traumatic or thermal injury are alterations in T cell activation, reduced lymphocyte interleukin-2 (IL-2) production, and associated depression of T lymphocyte proliferation. This study attempts to localize the cellular mechanisms underlying abnormal IL-2 production in thermal injury. METHODS: Following National Institutes of Health guidelines, 150 A/J mice were anesthetized, subjected to a 20% full-thickness scald burn injury or sham burn, and killed at intervals from 4 to 21 days later; splenocytes were harvested for in vitro studies. For measurement of IL-2 production, cells were cultured with either concanavalin A or a combination of the phorbol ester PMA, which directly activates protein kinase C, and the calcium ionophore A23187, which increases intracellular calcium. Cytokine mRNA expression was measured by Northern blot analysis and IL-2 production by bioassay. RESULTS: Both IL-2 production and IL-2 mRNA expression were consistently suppressed in concanavalin A-stimulated cells from burned mice compared with sham burns. This suppression of IL-2 and IL-2 mRNA also occurred when T cells were activated with PMA and A23187, bypassing the earlier stages of the signal transduction mechanism. IL-1 beta and tumor necrosis factor-alpha mRNA expression were consistently increased in burned animals, indicating that decreased IL-2 mRNA expression was specific to IL-2 and not representative of a global decrease in cytokine mRNA expression. CONCLUSIONS: These results suggest that the principal cellular abnormalities that result in altered T cell activation and IL-2 production after thermal injury lie downstream of the initiating signal transduction events and before IL-2 gene transcription.

Ionotropic glutamate receptors in the retina: moving from molecules to circuits.

The cloning of the glutamate-gated ion channels of the brain revealed an unexpected level of complexity: there are many different genes that encode distinct subunits of the receptor/channel complex and an even larger number of possible receptor subunit combinations. Many--nearly all--of these gene products are expressed in the retina, and the questions that we face today are: how are they used and why are there so many? Answers to these questions will be found at several levels. At the level of transcription, we have learned that different sets of subunits are expressed by different retinal neurons. Little is known about the transcriptional control of these genes, so it remains to be determined whether these patterns of expression reflect the need for different gene products in different retinal neurons or whether these patterns of expression reflect the functional constraints of gene expression. Another level of complexity is caused by alternative splicing, and here we report that at least four and possibly all eight of the different NMDAR1 transcripts are present in the mouse retina. The consequences of this alternative splicing are poorly understood, but antibodies directed against the two different possible C-termini of NMDAR1 label many of the same cell types. It is possible that these different splice variants are combined to generate the channels. While immunohistochemistry provides us with a glimpse of the subunit proteins, much remains to be learned about their half-life within a retinal cell, their intracellular trafficking, their regulation at the synapse, and the proteins associated with their cytoplasmic domains. An approach we have taken towards studying the dynamic properties of receptor subunits has been to fuse them to the cDNA encoding the jellyfish Green Fluorescent Protein. This makes it possible to follow functional subunits in transfected cells over time and to begin to measure the mobility of the protein.

Binary oscillatory cross-flow electrophoresis: theory and experiments.

In this article a novel electrophoretic separation technique, Binary Oscillatory Cross-flow Electrophoresis (BOCE), is described. The technique utilizes the interaction of an oscillatory electric field and a transverse oscillatory shear flow to create an active binary filter for the separation of charged protein species. An oscillatory electric field is applied across the narrow gap of a rectangular channel inducing a periodic motion of charged protein species. The amplitude of this motion depends on the dimensionless electrophoretic mobility, alpha = Eomu/omegad, where Eo is the amplitude of the electric field oscillations, mu is the dimensional mobility, omega is the angular frequency of oscillation, and d is the channel gap width. An oscillatory shear flow of the form u = Deltaxomega(beta + cos(2omegat)) where beta is the fraction of steady flow and Deltax is the tidal displacement, is induced along the length of the channel resulting in the separation of species with different mobilities. An analytic model is presented that predicts the induced convective velocity of solute species as a function of alpha and beta in the absence of diffusion. Numerical simulations including diffusion support these predictions, and determine the time history of the concentration profiles in a separation cell and connecting reservoirs. In experiments using a model protein system including bovine serum albumen (BSA) and bovine hemoglobin (BHb), solute throughputs of 37 mg/h of 92% pure BSA have been observed in a small separation cell with a volume of 3 mL. These results are in close agreement with theoretical predictions.

Impact of video colonoscopy on stage and outcome of patients with symptomatic colorectal cancer.

BACKGROUND: Double-contrast barium enema still is regarded by many as the investigation of choice for patients with large bowel symptoms. The aim of this study was to compare the stage and outcome of patients with colorectal cancer diagnosed by video colonoscopy (VC) and barium enema (BE) in a single institution. METHODS: Between July 1997 and December 2001, data were gathered prospectively in a series of 489 patients presenting consecutively with symptomatic colorectal cancer. Selection of patients for either VC or BE investigation was made by the clinician who examined the patient in the clinic. Of the 489 patients, 82 were excluded because they presented acutely or other methods were used for the diagnosis. RESULTS: A diagnosis of colorectal cancer was determined by VC for 292 patients and by BE for 115 patients. The patients in both groups were similar in terms of age, gender, and site of disease. Stage 1 disease (T1/2NO) was diagnosed for 87 (29.8%) patients in the VC group, as compared with 10 (8.7%) in the BE group (p < 0.0001). Early colorectal cancer (T1) was diagnosed for 43 patients in the VC group as compared to 1 patient in the BE group (p < 0.0001). During a median follow-up period of 33 months, 8.2% of the patients in the VC group had experienced recurrence after curative resection, as compared with 17.4% of the patients in the BE group p = 0.018). Freedom from disease (p = 0.02) and overall survival (p = 0.03) were significantly increased in the VC group. CONCLUSIONS: Videocolonoscopy used as the investigation of choice for patients with large bowel symptoms detects colorectal cancer at an earlier stage and has a significant impact on the outcome for this condition.

Prevalence of osteoporosis in women referred for bone density testing: utility of multiple skeletal sites.

The objective of this study was to determine retrospectively the prevalence of osteoporosis in a referral population and to compare the effectiveness of measuring multiple skeletal sites for identifying osteoporosis. Although osteoporosis is considered to be a major public health problem in the United States, and there are reliable methods for diagnosis based on bone densitometry, fewer than 25% of cases are currently identified. There is no consensus about which skeletal site(s) should be measured for optimal results. In this study, bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) at the radius (proximal site), lumbar spine, femoral neck, and total proximal femur regions in 537 consecutive white females age 50 and older referred by community physicians for bone densitometry. The prevalence of osteopenia and osteoporosis (based on the World Health Organization definitions) was determined, as well as the incidence of misclassification of patients based on different skeletal sites. Overall, 53.3% had osteoporosis, an additional 37.7% had osteopenia, and only 8.7% had normal BMD at all measurement sites. The prevalence was similar at all measurement sites and the incidence of misclassification was low. Given the magnitude of undetected osteoporosis and the efficacy of bone densitometry at any skeletal site, these data have important implications for the optimal deployment of bone density measurement facilities.

A35512, a complex of new antibacterial antibiotics produced by Streptomyces candidus. II. Chemical studies on A35512B.

The glycopeptide antibiotic A35512B was isolated from Streptomyces candidus NRRL 8156 as the major active factor. Chemical degradation studies showed that mild hydrolysis resulted in the release, one molecule each, of four neutral sugars: rhamnose, fucose, glucose and mannose, as well as the liberation of a complex peptide core which retained all the amino acids and from which 3-amino-2,3,6-trideoxy-3-C-methyl-L-xylo-hexopyranose, a new amino sugar, was isolated (2). Oxidative degradation of A35512B resulted in the isolation of a chlorodiphenylether (5), dimethyl 4-methoxyisophthalate (7) and methyl 3,5-bis-(4-methoxycarbonylphenoxy(-4-methoxybenzoate (6). The structure of 5 could not be conclusively elucidated but was shown to be either 5-chloro-2',3-dimethoxy-2,5'-dicarbomethoxy diphenylether (5a) or 2-chloro-2',3-dimethoxy-5,5'-dicarbomethoxy diphenylether (5b) by physical methods. This halogenated fragment was shown to arise from oxidation of constituent amino acid (10) which has the aromatic substitution pattern of fragment (5a or 5b). Base hydrolysis resulted in the isolation of a phenanthridine (9) which arose from 2',4,6-trihydroxybiphenyl-2,5'-diyldiglycine. These chemical degradation studies on A35512B showed that this antibiotic is closely related to the ristocetin class of antibiotics.

A54145, a new lipopeptide antibiotic complex: microbial and chemical modification.

A54145 is a complex of acidic lipopeptide antibiotics produced by Streptomyces fradiae NRRL 18158, NRRL 18159, and NRRL 18160. Each antibiotic factor consists of a peptide core bearing an N-terminal acyl substituent. N-Lys-tert-BOC-protected A54145 complex was deacylated by Actinoplanes utahensis; three protected core peptides were isolated. A54145 antibiotic analogs were synthesized by acylation of the tryptophan N-terminus with 2,4,5-trichlorophenyl active esters, followed by deblocking with trifluoroacetic acid.

Actaplanin, new glycopeptide antibiotics produced by Actinoplanes missouriensis. The isolation and preliminary chemical characterization of actaplanin.

Actaplanin (A4696), a new complex of broad spectrum Gram-positive antibiotics is produced by Actinoplanes missouriensis. High performance liquid chromatography was used to show that this complex is composed of several actaplanins. Hydrolytic experiments with acetaplanins A, B1, B2, B3, C1 and G showed that these actaplanins were composed of the same peptide core, an amino sugar and varying amounts of glucose, mannose and rhamnose. The neutral sugar content was determined for each actaplanin. A bioautographic study of aglycone formation during hydrolysis of the actaplanin complex showed that within a short time a simple mixture of two antimicrobially active hydrolysis products was obtained. These substances retained the antimicrobial spectrum and a high percentage of the antibiotic activity of the parent actaplanin complex. Methanolysis of the acetaplanin complex as well as the individual actaplanins resulted in the selective loss of the neutral sugar moieties and the isolation of actaplanin psi (pseudo)-aglycone--the core peptide which still retained an amino sugar group. The 1H NMR spectrum of this substance indicated a similarity to many features of ristocetin psi-aglycone. Hydrolytic studies showed that the amino sugar present in actaplanin was identical with L-ristosamine. It is concluded that the aglycone of actaplanin is a complex peptide composed of aromatic amino acids, and that the actaplanins each possess this aglycone and L-ristosamine but are differentiated by their neutral sugar composition.