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Summary A pilot study was conducted to test the use of accelerometer tags (coded acoustic transmitters equipped with inertial sensors) to detect changes in green sturgeon activity following gillnet capture and release. Green sturgeon Acipenser medirostris (Ayres, 1854) is listed as threatened under the Endangered Species Act, but is captured as bycatch in both estuarine and coastal gillnet and trawl fisheries. Measured were tailbeat activity and swimming depth of sturgeon (145-167 cm fork length) caught with gillnets in Willapa Bay, Washington during late July 2011. These data were transmitted acoustically over a period of up to 55 d to an array of 16 receivers positioned in the bay. Transmitters were either surgically implanted (n = 2) or attached externally to the dorsal scutes (n = 2). In spite of the small number of fish tagged, over 4,800 data transmissions were obtained, with three fish detected over more than 46 d and in estuaries up to 55 km from the release site. Breakpoint regression analysis indicated that the accelerometers could be used to document discrete changes in activity of the fish after handling. Use of this technology could therefore allow the identification of fishing methods that are most harmful to protected species.

Retinol (vitamin A) is an example of a small molecule that is essential for higher organisms; its utilisation has been involved in the evolution of a number of proteins. In mammalian species, retinol is obtained from the diet and controls the release of its binding protein from hepatocytes into the blood stream. Subsequent influx into cells under normal situations usually involves a specific membrane-bound receptor for retinol-binding protein, which facilitates the uptake of retinol alone or bound to its carrier. This specific receptor has not yet been identified, but a receptor for a related lipocalin has been cloned. It represents a relatively new family, and there are a number of related genes in various eukaryotic genomes, suggesting that the system is very widespread in multicellular organisms. Its significance has been highlighted recently by the suggestion that retinol-binding protein, through its receptor, may play a major role in type 2 diabetes, perhaps the greatest scourge of modern society. This system may provide a new paradigm in mammalian biology, another example of which may exist in the processes responsible for steroid handling. This review outlines the characteristics of retinol utilisation in mammalian species, focusing primarily on the uptake system.

A generalized three-dimensional (3D) quantitative structure-property relationship (QSPR) formalism, based upon molecular shape analysis (MSA), has been applied to an analog series of pyridobenzodiazepinone inhibitors of muscarinic 2 (M2) and 3 (M3) receptors. The fundamental goal of this application is to establish MSA-3D-QSARs (P = A = inhibition activity) that are based upon identifying the active conformations of these flexible analogs. The repetitive use of partial least squares (PLS) analysis permits the construction of the MSA-3D-QSARs. In addition to molecular shape, the identification of the properties of a lipophilic binding site and specific nonallowed steric receptor sites govern the MSA-3D-QSARs. The M2 and M3 QSARs suggest receptor subtype specificity might be realized by targeting upon a specific nonallowed steric receptor site. One conformation, common to both M2 and M3 receptors, emerges as dominant in the optimum MSA-3D-QSARs. However, other similar conformations are also found to yield meaningful MSA-3D-QSARs.

A skeletal collection from the African country of Sudan was examined to determine if torsion of the tibia in an African population varies from established norms for European, Asian, and American populations. A large variation in tibial torsion was observed. There was a distinct limb asymmetry with more torsion on the right than left. No association of tibial torsion with gender was identified. A small but appreciable increase in average torsion (7°) was identified when this population was compared with previously reported populations. This study documents a variation in tibial torsion not appreciated in earlier studies. © 1994 Wiley-Liss, Inc.

Segmental renal artery branches within the renal sinus were prospectively evaluated with color Doppler imaging and pulsed-Doppler spectral analysis in 56 patients before angiography. Waveforms were evaluated for the tardus and parvus abnormalities of prolonged acceleration time, diminished acceleration index, and loss of the normal early systolic compliance peak/reflective-wave complex (ESP). Findings obtained with these parameters were compared with the subsequent findings on angiograms to ascertain their efficacy in detection of hemodynamically significant (greater than or equal to 60%) renal arterial stenosis (RAS), which was present in 32 kidneys in 26 patients. Simple pattern-recognition analysis of ESP proved to be the best of the three parameters. Loss of ESP enabled identification of RAS with 95% sensitivity, 97% specificity, a 92% positive predictive value, a 98% negative predictive value, a 96% overall accuracy. On the basis of the high technical success rate, high sensitivity and specificity, and short examination time, waveform analysis for detection of tardus-parvus abnormalities, especially loss of ESP, of the segmental artery is recommended as an alternative to direct examination of the main renal arteries for evaluation of RAS.

One hundred two patients with mammographically suspicious, nonpalpable lesions underwent stereotactic breast biopsy with a biopsy gun and an automated 14-gauge cutting needle. After biopsy, a localization wire was placed and surgical biopsy performed. There was agreement of the histologic results from the gun biopsy and the surgical biopsy specimens in 98 cases (96%), including 22 of 23 carcinomas (96%) (kappa = 0.936). The gun biopsy yielded findings that led to the correct diagnosis in two cases involving lesions that were missed at surgical biopsy; two lesions found at surgery were missed at gun biopsy. The results of this study suggest that the use of 14-gauge needles improves agreement between surgical and needle core biopsy findings and that stereotactic biopsy with an automated needle and gun can be an acceptable alternative to surgical biopsy in women with mammographically suspicious breast lesions.

Previous histological findings, physiological data, and behavioral observations on the A-type lamin knockout mouse (Lmna(-/-)) suggest that important aspects of this model resemble the human Emery-Dreifuss muscular dystrophy (EDMD) phenotype. The main goal of our experiments was to study skeletal and cardiac muscle function in this murine model to obtain the semiquantitative data needed for more detailed comparisons with human EDMD defects. Measurements of the mechanical properties of preparations from two different skeletal muscle groups, the soleus and the diaphragm, were made in vitro. In addition, records of the electrocardiogram, and measurements of heart rate variability were obtained; and phasic contractions (unloaded shortening) of enzymatically isolated ventricular myocytes were monitored. Soleus muscles from Lmna(-/-) mice produced less force and work than control preparations. In contrast, force and work production in strips of diaphragm were not changed significantly. Lead II electrocardiograms from conscious, restrained Lmna(-/-) mice revealed slightly decreased heart rates, with significant prolongations of PQ, QRS, and 'QT' intervals compared with those from control recordings. These ECG changes resemble some aspects of the ECG records from humans with EDMD; however, the cardiac phenotype in this Lmna(-/-) mouse model appears to be less well-defined/developed. Ventricular myocytes isolated from Lmna(-/-) mice exhibited impaired contractile responses, particularly when superfused with the beta-adrenergic agonist, isoproterenol (1 microM). This deficit was more pronounced in myocytes isolated from the left ventricle(s) than in myocytes from the right ventricle(s). In summary, tissues from the Lmna(-/-) mouse exhibit a number of skeletal and cardiac muscle deficiencies, some of which are similar to those which have been reported in studies of human EDMD.

One hundred three patients underwent stereotactic breast biopsy with an 18-, 16-, or 14-gauge cutting needle and a biopsy gun. After biopsy, a localization wire was placed and surgical biopsy performed. There was agreement of the histologic results in 89 cases (87%) including 14 of 16 cancers (87%) (kappa = 0.806). The gun biopsy yielded the correct diagnosis in four cases involving a lesion (including one cancer) that was missed at the surgical biopsy. Nine cases in which the lesion was missed at gun biopsy can be related to insufficient needle size, the greater difficulty in using one of the two stereotactic devices, and early inexperience with the technique. A 14-gauge needle was used in the last 29 biopsies, the results of which agreed with the surgical pathologic findings in 28 cases (97%). With greater experience, stereotactic-guided large-gauge automated percutaneous biopsy may prove to be an acceptable alternative to surgical biopsy in women with breast masses suspected at mammography.

Previous histological findings, physiological data, and behavioral observations on the A-type lamin knockout mouse (Lmna(-/-)) suggest that important aspects of this model resemble the human Emery-Dreifuss muscular dystrophy (EDMD) phenotype. The main goal of our experiments was to study skeletal and cardiac muscle function in this murine model to obtain the semiquantitative data needed for more detailed comparisons with human EDMD defects. Measurements of the mechanical properties of preparations from two different skeletal muscle groups, the soleus and the diaphragm, were made in vitro. In addition, records of the electrocardiogram, and measurements of heart rate variability were obtained; and phasic contractions (unloaded shortening) of enzymatically isolated ventricular myocytes were monitored. Soleus muscles from Lmna(-/-) mice produced less force and work than control preparations. In contrast, force and work production in strips of diaphragm were not changed significantly. Lead II electrocardiograms from conscious, restrained Lmna(-/-) mice revealed slightly decreased heart rates, with significant prolongations of PQ, QRS, and 'QT' intervals compared with those from control recordings. These ECG changes resemble some aspects of the ECG records from humans with EDMD; however, the cardiac phenotype in this Lmna(-/-) mouse model appears to be less well-defined/developed. Ventricular myocytes isolated from Lmna(-/-) mice exhibited impaired contractile responses, particularly when superfused with the beta-adrenergic agonist, isoproterenol (1 microM). This deficit was more pronounced in myocytes isolated from the left ventricle(s) than in myocytes from the right ventricle(s). In summary, tissues from the Lmna(-/-) mouse exhibit a number of skeletal and cardiac muscle deficiencies, some of which are similar to those which have been reported in studies of human EDMD.

Electrophoretically mediated microanalysis (EMMA) is a method of accomplishing chemical analyses, typically in an open-tubular capillary, due to the difference in the electrophoretic mobility between the particular reagents. This work reports on combining this technique onto microfabricated systems. Two methods of this technique were applied, constant potential and zero potential EMMA onto chips. A dosage response curve was run using this constant potential mode that resulted in a linear response over three orders of substrate concentration magnitude. The chemical system used here is beta-galactosidase (beta-Gal) as the enzyme and fluorescein mono-beta-D-galactopyranoside (FMG) as the substrate. The zero potential mode was used to amplify product turnover using various incubation times. Using this technique and a 10 min incubation, approximately 40000 enzyme molecules could be detected. The zero potential mode is also used in conjunction with an internal standard to show how one can quantitate using this method. The power and ease of utility of this technique is described.

C ray-scale and color Doppler sonography have proven useful in examining patients with acute scrotal pain and swelling [1, 2]. In this clinical setting, characterization of testicular blood flow enables more confident discrimination between those patients requiring urgent surgical treatment (testicular torsion) and those best treated noninvasively (e.g., epididymo-orchitis). Definitive diagnosis is more problematic when torsion is intermittent or incomplete. We present a case of partiab torsion of the spermatic cord in which a normal color Doppler flow pattern was observed in the testes; the hemodynamic changes associated with torsion were evident only on Doppler spectral analysis. In addition, this case is unusual in that there was direct visualization of the twisted spermatic cord and its accompanying vessels.

We wished to assess whether urodynamic changes accompanying normal pregnancy altered the pattern of ureteral jets, complicating detection of pathologic obstruction.Ureteral jets were observed with color Doppler sonography for 5 minutes in 26 women in the second or third trimester of pregnancy and in 6 non-pregnant controls (3 men and 3 women).A mean of 5.5 jets/minute were detected in the pregnant subjects, and the mean difference in frequency of jets between the right and left sides was 42%. Corresponding results for controls were 7.6 jets/minute and 11%, respectively. The 2 groups were significantly different with respect to jet symmetry (p0.02). Unilateral absence of jets was noted in 4 pregnant women but in no controls.Because of variation in ureteral jet bilaterality and symmetry during the later stages of pregnancy, caution is recommended in the use of the technique to diagnose obstructive urolithiasis in this population.

Traditional images of the distal femur place the intercondylar groove midway between the condyles. The location of the sulcus of the intercondylar groove in a large Sudanese skeletal population was verified using a custom stereotactic device. The results of this study show that the femoral sulcus is lateral to the midplane between the 2 femoral condyles. This study also shows that the configuration of the sulcus is linear and is oriented between the traditional anatomic and mechanical axes of the femur.

Human aminoacylase-1 (N-acyl-L-amino-acid amidohydrolase, EC 3.5.1.14; ACY1) is a homodimeric zinc-binding enzyme that catalyzes the hydrolysis of N alpha-acylated amino acids. ACY1 has been assigned to chromosome 3p21.1, a region reduced to homozygosity in small cell lung cancer (SCLC), and has been reported to exhibit reduced or absent expression in SCLC cell lines and tumors. Two human cDNA libraries and one human genomic DNA library were screened with a previously isolated partial ACY1 cDNA to isolate a full-length transcript. Sequence analysis of clones from each of these libraries resulted in an ACY1 cDNA of 1438 base pairs with an open reading frame of 1224-base pairs coding for a putative protein of 408 amino acids with a predicted molecular mass of 45,882 Da. Sequence analysis revealed no homologies to previously reported cDNA or protein sequences and establishes ACY1 as the first member of a new family of zinc-binding enzymes to be so characterized. The subcellular location of ACY1 has been established as cytosolic by flow cytometry. Southern and northern analyses of ACY1 in SCLC cell lines failed to demonstrate any gross abnormalities of the ACY1 structural gene or instances of absent or aberrantly sized mRNA, respectively.

A linear benchmark between the linear ideal MHD stability codes ELITE [H. R. Wilson et al., Phys. Plasmas 9, 1277 (2002)], GATO [L. Bernard et al., Comput. Phys. Commun. 24, 377 (1981)], and the extended nonlinear magnetohydrodynamic (MHD) code, NIMROD [C. R. Sovinec et al.., J. Comput. Phys. 195, 355 (2004)] is undertaken for edge-localized (MHD) instabilities. Two ballooning-unstable, shifted-circle tokamak equilibria are compared where the stability characteristics are varied by changing the equilibrium plasma profiles. The equilibria model an H-mode plasma with a pedestal pressure profile and parallel edge currents. For both equilibria, NIMROD accurately reproduces the transition to instability (the marginally unstable mode), as well as the ideal growth spectrum for a large range of toroidal modes (n=1–20). The results use the compressible MHD model and depend on a precise representation of “ideal-like” and “vacuumlike” or “halo” regions within the code. The halo region is modeled by the introduction of a Lundquist-value profile that transitions from a large to a small value at a flux surface location outside of the pedestal region. To model an ideal-like MHD response in the core and a vacuumlike response outside the transition, separate criteria on the plasma and halo Lundquist values are required. For the benchmarked equilibria the critical Lundquist values are 108 and 103 for the ideal-like and halo regions, respectively. Notably, this gives a ratio on the order of 105, which is much larger than experimentally measured values using Te values associated with the top of the pedestal and separatrix. Excellent agreement with ELITE and GATO calculations are made when sharp boundary transitions in the resistivity are used and a small amount of physical dissipation is added for conditions very near and below marginal ideal stability.

We performed a retrospective study of symptomatic peripheral vascular malformations to determine if MR imaging can be used to distinguish slow-flow venous malformations from high-flow arteriovenous malformations and arteriovenous fistulas. Twenty-seven MR examinations in 25 patients with malformations outside the CNS were reviewed. Sixteen venous malformations, nine arteriovenous malformations, and two arteriovenous fistulas were included. In all cases, the MR findings were correlated with the results of angiography. The distinction between slow-flow venous malformations and high-flow arteriovenous malformations and arteriovenous fistulas was made primarily on T2-weighted MR images, which showed high signal intensity in venous malformations and flow voids in high-flow lesions. In addition to the previously described MR features of venous malformations (serpentine pattern with septations, associated muscle atrophy, and typical T1 and T2 signal intensities), several new MR features were apparent. Venous malformations had a propensity for multifocal involvement (37%), orientation along the long axis of extremities or affected muscles (78%), and adherence to neurovascular distributions (64%). Prominent subcutaneous fat was commonly seen adjacent to the malformation. MR images of arteriovenous malformations and arteriovenous fistulas also commonly showed muscle atrophy and subcutaneous fatty prominence. Our results show that slow-flow venous malformations can be distinguished from high-flow arteriovenous malformations and fistulas on the basis of spin-echo MR signal characteristics. The associated imaging characteristics help in the differential diagnosis in problematic cases.

Body space measurements using simultaneous multiple isotope dilution techniques were made in both hyponatraemic and normonatraemic patients with carcinoma of the bronchus and wasting, and compared with those in a group of normal volunteers. Both groups of patients showed osmolal loss from cells. The significance of these findings in relation to the development of hyponatraemia is discussed.

This presentation focuses upon developing methods to postulate active conformations/shapes in a series of flexible analogs when the receptor geometry is unknown. In one study of a set of 3-X substituted triazines which inhibit dihydrofolate reductase (DHFR), the size and flexibility of the substituents were both too large, and the number of analogs and substituent structural changes each too small, to permit a reliable inference of the active substituent conformation. However, use of template conformations from ligands bound to DHFR, along with minimum energy substituent conformations, permitted us to postulate that the bonding topology of the substituent, and not its conformation, controls the SAR. In another study of a series of β-hydroxylase inhibitors it was possible to construct a molecular shape descriptor that employs loss in intramolecular conformational energy as part of the shape comparison. In both cases significant 3D-QSARs were generated and the methods developed were added to our molecular shape analysis (MSA) formalism.

6013 Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers and preclinical data has demonstrated possible synergy with platinums and taxanes. Treatment options for recurrent/metastatic HNSCC are limited. A study of cisplatin and docetaxel showed a response rate of 40% and 9.6 month median survival. Erlotinib, an EGFR tyrosine kinase inhibitor, had a 4.3% response rate as single agent in HNSCC. Because of the possible synergy and efficacy, we proposed to study the combination of cisplatin, docetaxel and erlotinib in advanced HNSCC. Methods: Patients (pts) were required to have adequate performance status, measurable disease, no prior EGFR therapy, and may have received prior induction, concomitant or adjuvant chemotherapy, but not for recurrent/metastatic disease. Sites of disease included squamous cell head and neck sites excluding nasopharynx and sinus. Treatment included docetaxel 75 mg/m2 and cisplatin 75 mg/m2 intravenously every 3 weeks and erlotinib 150 mg by mouth daily. All agents were started on day 1. Pts were treated with growth factor support. Results: The trial has completed accrual to 50 pts. 47 pts are available for analysis at this time. Median age is 56 years (range 39–72). ECOG PS is 0, 1, 2 (6, 29, 2 pts). 43 pts are evaluable for efficacy. All responses were confirmed via RECIST. Complete responses have been in observed in 4 pts, partial responses in 25 pts and 12 pts have stable disease for an overall response rate of 67% and disease control rate of 95%. After a follow-up of 19 months, median overall survival was 11 months (8.61, 22.5, 95% CI) and progression free survival was 6.01 months (4.37, 8.25). 6 pts had grade 3/4 febrile neutropenia, 4 pts had grade 3/4 dehydration, 3 pts had grade 3 diarrhea, and 2 pts had grade 3/4 GI bleeding. The most common grade 1–2 toxicities were diarrhea, nausea, and rash. Conclusions: The combination of cisplatin, docetaxel and erlotinib is well tolerated and has very encouraging activity in recurrent/metastatic HNSCC. Tissues are being collected and analyzed for correlative markers including downstream EGFR pathway markers (p-akt, mek, k-ras). Final efficacy and biomarker results will be presented at the annual meeting. No significant financial relationships to disclose.

18538 Background: Erlotinib is an oral epidermal growth factor receptor (EGFR) targeted therapy. It is approved for therapy in NSCLC pts after failure of at least one prior chemotherapy regimen, and in combination with gemcitabine for pts with pancreatic cancer. It has also been studied in other tumors including HNC. Erlotinib has fewer side effects compared to standard chemotherapy. Cutaneous toxicities with erlotinib have been observed in approximately 70% of pts with most cases typically mild-to-moderate. The most common manifestations are an acneiform rash, pruritus, and dryness. As rash may be a marker of clinical benefit, continuing therapy through toxicities is important. Methods: We have described effective management of skin rash associated with erlotinib by using the proposed treatment algorithm in HNC pts enrolled in a phase II study in which they received erlotinib with chemotherapy. Pts were followed by physical exams and direct questionings about rash development and treatment response as they were treated based on the grade and characteristics (pruritic, macular, pustular, dryness, ulcerative) of rash. Results: Thus far, the HNC trial has enrolled 32 pts and 28 pts are evaluable for rash and treatment responses. 19 pts developed grade 1 rash, 8 pts grade 2, 1 pt grade 3, and none grade 4. Response to rash intervention (ie downgrading the rash) included 19/19 complete responses for grade 1, 6/8 partial responses for grade 2 (the non-responding patients were referred to dermatology and improved after several other treatments) and 1/1 partial response for grade 3 were noted. 4 pts experienced dose delay and/or dose modification. In addition, 33 NSCLC pts are also evaluable for toxicity. 25 pts developed grade 1 rash, 4 pts grade 2, 4 pts grade 3, and none grade 4. Response to rash intervention included 25/25 complete responses for grade 1, 4/4 complete/partial responses for grade 2 and 3. Four pts experienced dose delays and/or dose modifications. Conclusions: Successful management of rash associated with erlotinib can be achieved using the proposed treatment algorithm thus allowing pts to continue on treatment without delays or significant dosing changes. [Table: see text]

5521 Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers and preclinical data has demonstrated possible synergy with platinums and taxanes. Treatment options for advanced or recurrent HNSCC are limited. A study of cisplatin and docetaxel showed a response rate of 40% and 9.6 month median survival. Erlotinib, an EGFR tyrosine kinase inhibitor, had a 4.3% response rate in HNSCC. Because of the possible synergy and efficacy, we proposed to study the combination of cisplatin, docetaxel and erlotinib in advanced HNSCC. Methods: Patients (pts) were required to have adequate performance status, measurable disease, no prior EGFR therapy, and may have received one regimen of induction, concomitant or adjuvant chemotherapy, but not for recurrent/metastatic disease. Sites of disease included squamous cell head and neck sites excluding nasopharynx and sinus. Treatment included docetaxel 75mg/m2 and cisplatin 75mg/m2, intravenously every 3 weeks and erlotinib 150 mg by mouth daily. Patients were treated with growth factor support. Results: 37 pts have been enrolled thus far. Median age is 56 years (range 39–72). Median ECOG PS is 1 (range 0–2). 32 pts are evaluable for confirmed response using RECIST criteria. Complete responses have been in observed in 3 pts, partial responses in 18 pts and 8 pts have stable disease for an overall response rate of 66% and disease control rate of 91%. Only 2 pts progressed after 2 cycles of treatment. 5 pts had grade 3/4 neutropenia (2 febrile),1 pt had grade 4 diarrhea, and 2 pts had grade 3 rash. The most common grade 1–2 toxicities were diarrhea, nausea, and rash. Conclusion: The combination of cisplatin, docetaxel and erlotinib is well tolerated and has very encouraging activity in advanced HNSCC. Data collection for response rate, duration of response and survival is ongoing. Trial accrual continues up to 50 patients and biopsies are being collected for correlative markers including downstream EGFR pathway markers (p-akt, mek, k-ras). The full data set will be presented at the annual meeting. [Table: see text]

5565 Background: Treatment options for advanced disease are limited and for those patients failing chemotherapy, there are few viable options. Lonafarnib is a novel tricyclic peptidomimetic compound that is a potent and specific inhibitor of farnesyl protein transferase. We have previously reported clinical activity of lonafarnib in untreated HNSCC (4 of 22 patients showed response despite drug exposure for only 7–14 days). We proposed to assess the activity of lonafarnib in advanced HNSCC patients. Methods: An open-label phase II single-center study was conducted to determine the objective response rate of lonafarnib administered at 200 mg bid, enrolling patients who were incurable and who failed at least one platinum-containing regimen, but received no more than three prior regimens. Results: Fifteen patients, aged 32 to 66 (median age 57) were enrolled. All patients had baseline ECOG PS 0 or 1. Median treatment duration was 61 days (range 0–224 days). Median time to progression was 62 days. No objectiv...

5515 Background: We have conducted a phase II trial of induction chemotherapy (CT) consisting of 3 treatment cycles with paclitaxel 175 mg/m2 day 1; ifosfamide 1000 mg/m2 IV daily x 3; and carbopla...

8231 Background: Therapies targeting the epidermal growth factor receptor (EGFR) including small molecule inhibitors have promise but are accompanied by side effects, predominantly rash. As rash ma...

SummaryProstaglandin E2 pessaries for the induction of labour are being used more in ‘high-risk' cases and may have advantages for the diabetic patient. Prostaglandin E2 is known to cause decreased glucose-induced insulin secretion in diabetes mellitus. We did not detect adverse effects of clinical importance in a preliminary study of diabetic patients using prostaglandin E2 vaginal pessaries before induction of labour.

SummaryTotal glycosylated haemoglobin (Hb A1 (a + b + c)) was measured several times during the third trimester of pregnancy in 40 insulin-treated diabetics and the results compared with the patients' glucose control and fetal outcome. In spite of poor glucose control, 2 patients were found who had normal glycosylated haemoglobin levels throughout; both produced macrosomic babies who became hypoglycaemic. Conversely, 4 patients with apparently good inpatient glucose control were found to have abnormal glycosylated haemoglobin and also delivered abnormal infants. Poor fetal outcome in terms of macrosomic or hypoglycaemia and high cord C-peptide concentration reflecting pancreatic β-cell hyperplasia was sufficiently well associated with abnormal glycosylated haemoglobin concentration to conclude that its measurement is a useful additional test for monitoring diabetic pregnancy

SummaryThe outcome of pregnancies of 34 diabetic women treated as outpatients with regular home blood glucose monitoring was found to be similar to that in an earlier series of 27 women whose diabetes was managed by repeated hospital admissions. Outpatient management has clear advantages in terms of patient convenience and cost.

The history and the clinical and necropsy findings are presented of a patient who died from Aspergillus fumigatus pyaemia occurring as an opportunistic infection complicating a dissecting aortic aneurysm. The diagnosis was made (and treatment instituted) during life: it rested upon repeated isolation of the organism from tracheal aspirations, a positive blood culture and positive serum precipitin reactions to A. fumigatus. Debilitating disease along with large doses of antibiotics and corticosteroids provided the conditions necessary for the normally saphrophytic fungi to become pathogenic. As the therapy for aspergillosis is still ineffective, the danger of prescribing large doses of antibiotics together with corticosteroids is stressed.

A randomized double blind trial of insulin and glibenclamide treatment vs insulin and placebo was carried out in 20 insulin-dependent diabetics. Nine patients were C-peptide secretors and all increased their C-peptide output during a 50 g OGTT at the end of the insulin and glibenclamide treatment period by a mean of 47%. At the same time their mean daily blood glucose fell from 8.4 ± 1.7 to 7.4 ± 1.5 mmol/l and their HbA1 from 8.1 ±0.5 to 7.5 ±0.9% (mean ± sd). There was no change in any of the measurements of diabetic control in C-peptide non-secretors and no evidence for any extrapancreatic effects of glibenclamide in this group of patients. Combined insulin and glibenclamide treatment may produce a useful improvement of diabetic control in insulin-dependent diabetics who still secrete some endogenous insulin, although further studies are required.

Summary A patient who developed priapism 7 hr after stopping an intravenous heparin infusion is described. Abnormal spontaneous platelet aggregation was demonstrated whilst on heparin treatment and is thought to play a role in the aetiology of heparin induced priapism.

An assessment of the metabolic effect of dietary carbohydrate on daily insulin secretion, reflected by the 24-h urine output of C-peptide, has been made. Urinary C-peptide excretion increased when the carbohydrate intake of 6 normal subjects was increased from 200 to 400 g. A high-fibre diet rich in beans and lentils caused a significant fall in urine C-peptide and a lowering of blood glucose values in both normal and diabetic subjects. This confirms the insulin-sparing effect of leguminous foods. An increase of dietary fibre to 50 g mainly as cereal fibre did not significantly alter urine C-peptide excretion in normal subjects. Urinary C-peptide estimations could be useful for assessing the effect of different diets on daily insulin secretion.

Residual insulin secretion, reflected by the presence of C-peptide in serum and urine, has been demonstrated in 5 of 10 insulin-requiring diabetics of less than 10 years' duration tested. The C-peptide response, in the C-peptide secretors, showed a significant increase in both serum and urine after 4 weeks' treatment with 15 mg glibenclamide daily in addition to their usual insulin regime although no beneficial effects in metabolic control were detected. It is suggested that glibenclamide might be a useful adjunct to insulin therapy in insulinrequiring diabetics who still secrete C-peptide.

Stereotaxic core biopsy provides intact samples of breast tissue for accurate histologic analysis. We conducted a study to determine if prognostic data could also be successfully derived from such core samples and how the data correlate with surgical biopsy.Both core and surgical breast biopsies from 135 patients were processed under a uniform flow cytometry protocol. Samples were coded and then randomly processed at an outside flow cytometer and interpreted by an independent pathologist; the code was broken and patients' results correlated only after all samples were completely analyzed.Core breast biopsy provides intact tissue that can be successfully processed by a flow cytometer, even after being embedded in paraffin for initial histologic analysis. Larger cores (14 gauge) had fewer insufficient samples, as recorded on ploidy histograms. Although ploidy may reflect the underlying aggressiveness of a lesion and assist in evaluating breast cancer, surgical-pathologic correlation with stereotaxic biopsy indicated, as has been confirmed in other studies, considerable overlap of different ploidy types between benign and malignant conditions. There was no correlation between mammographic presentation and ploidy or S-phase fractions.Stereotaxic large-core biopsy can enable accurate histologic diagnosis of breast disease and furnish sufficient tissue for flow cytometric measurements of ploidy and S-phase fractions, even at an interval following paraffinization. Such prognostic information aids in planning of adjuvant therapy, allows flexibility should surgery fail to provide enough tissue for DNA study, and helps radiologists further market stereotaxic biopsy to clinicians.

A diabetic mother produced twins dissimilar in both appearance and blood biochemistry—one being clearly macrosomic and "hyperinsulinised" at delivery, the other apparently normal. It is suggested that the development of fetal hyperinsulinism may depend not only on maternal blood-glucose control but also on fetal blood-supply or genetic factors.

Summary A patient presenting with subarachnoid haemorrhage and high lipid concentrations in the cerebrospinal fluid (taken at lumbar puncture), who has later shown to have type V hyperlipidaemia is described. This case, so far as can be ascertained by the authors, is the first report of hyperlipidaemia being diagnosed from CSF examination.