Radioisotopic Procedure Research Articles

The additional role of 18F-FDG PET/CT in prosthetic valve endocarditis.

The purpose of the present review is an update on the diagnosis of prosthetic valve endocarditis (PVE), evaluating the additional value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to the standard modified DUKE criteria on which for a long time is based the diagnostic strategy of the disease. We did a comprehensive research on the studies reported in the literature and regarding the employment of 18F-FDG PET/CT in the early diagnosis of PVE in patients with suspected disease. Scientific databases have been examined such as Medline and PubMed, followed by a review of citations and reference lists. The research included the following terms: infective endocarditis, prosthetic heart valve and cardiac valve replacement infections, 18F-FDG PET/CT and endocarditis. The recent studies reported in the literature on the PVE diagnostic approaches showed elevated sensitivity and specificity values of 18F-FDG PET/CT ranging from 73 to 96.6% and from 80 to 94%, respectively, reducing the number of misdiagnosed patients. The usefulness of the radioisotopic procedure is even more important when the other diagnostic conventional diagnostic tools, such as echocardiography, are inconclusive or negative in patients in whom the diagnosis of PVE is definitively ascertained. However, false negative and positive results of 18F-FDG PET/CT were also ascertained in some studies interfering with image interpretation even if such limitation can be reduced with an adequate patient preparation, with a better knowledge of clinical course of the disease, of the treatment in progress and of the different technical aspects of the method. In different studies reported in the literature, 18F-FDG PET/CT proved to improve the diagnostic accuracy of the conventional modified DUKE criteria in patients with suspected IE, and in particular with PVE, giving the highest diagnostic performance and providing additional diagnostic benefits. Thus, the radioisotopic hybrid procedure should be included in the diagnostic protocol of PVE as complementary tool to modified DUKE criteria. Finally, the usefulness of 18F-FDG PET/CT in monitoring the response to antibiotic therapy, although the few data reported in the literature are encouraging, needs more numerous studies and with a major number of cases.

Ionizing Radiation Measurement Solution in a Hospital Environment.

Ionizing radiation is one of the main risks affecting healthcare workers and patients worldwide. Special attention has to be paid to medical staff in the vicinity of radiological equipment or patients undergoing radioisotope procedures. To measure radiation values, traditional area meters are strategically placed in hospitals and personal dosimeters are worn by workers. However, important drawbacks inherent to these systems in terms of cost, detection precision, real time data processing, flexibility, and so on, have been detected and carefully detailed. To overcome these inconveniences, a low cost, open-source, portable radiation measurement system is proposed. The goal is to deploy devices integrating a commercial Geiger-Muller (GM) detector to capture radiation doses in real time and to wirelessly dispatch them to a remote database where the radiation values are stored. Medical staff will be able to check the accumulated doses first hand, as well as other statistics related to radiation by means of a smartphone application. Finally, the device is certified by an accredited calibration center, to later validate the entire system in a hospital environment.

123I-ioflupane brain SPECT and 123I-MIBG cardiac planar scintigraphy combined use in uncertain parkinsonian disorders.

We evaluated the clinical usefulness of the combined use of 123I-ioflupane brain single photon emission computed tomography (SPECT) and 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy in discriminating uncertain parkinsonism with vascular lesions in striatal nuclei at magnetic resonance imaging (MRI). Forty-three consecutive patients with uncertain parkinsonism and vascular lesions at MRI in striatal nuclei were retrospectively evaluated; the uncertain differential diagnosis was between Parkinson's disease and vascular parkinsonism (PD/VP) in 22 patients, between PD and other neurodegenerative parkinsonism (PD/PS) in 11 patients and between Lewy body dementia and Alzheimer disease (LBD/AD) in the remaining 10 cases. All patients underwent 123I-ioflupane SPECT with striatal dopaminergic activity determination as binding potentials (BP; cut-off: 3.3). 123I-MIBG cardiac planar scintigraphy was performed 2 weeks later, in early (15 minutes) and delayed (240 minutes) phases also calculating heart to mediastinum (H/M) ratio (cut-off: 1.56). 123I-Ioflupane uptake was normal in 9 patients with BP values >3.3, while it was reduced in 34/43 cases with BP values <3.3 at least in one of the striatal nuclei. 123I-MIBG uptake was normal in 21/43 patients (5 of whom with normal and 16 with 123I-ioflupane striatal defects) showing the H/M ratio >1.56 in all cases; the uptake was reduced in 22/43 cases, (4 of whom were normal and 18 were with 123I-ioflupane striatal defects) with the H/M ratio <1.56 in all cases. No statistical differences were found when early and delayed H/M ratios were mutually compared. Combining the 2 radioisotopic procedures, a more reliable diagnosis was achieved in 39/43 cases properly classifying 13 PD, 10 VP, 7 PS, 5 LBD, and 4 AD. However, the diagnosis remained uncertain in four patients with normal 123I-ioflupane and reduced 123I-MIBG uptake. The results of the present study confirmed that in uncertain parkinsonian syndromes associated with vascular lesions in striatal nuclei, brain 123I-ioflupane SPECT alone did not prove able to discriminate between the different forms of disease. Only the association with 123I-MIBG cardiac scintigraphy, also with the early acquisition alone, allowed the most appropriate diagnosis in 90.7% of our cases. However, patients with normal 123I-ioflupane and reduced 123I-I-MIBG uptakes need a close clinical and instrumental follow-up as sympathetic damage could precede striatal disorders in the early stage of PD and LBD.

Nuclear medicine practices in the 1950s through the mid-1970s and occupational radiation doses to technologists from diagnostic radioisotope procedures.

Data on occupational radiation exposure from nuclear medicine procedures for the time period of the 1950s through the 1970s is important for retrospective health risk studies of medical personnel who conducted those activities. However, limited information is available on occupational exposure received by physicians and technologists who performed nuclear medicine procedures during those years. To better understand and characterize historical radiation exposures to technologists, the authors collected information on nuclear medicine practices in the 1950s, 1960s, and 1970s. To collect historical data needed to reconstruct doses to technologists, a focus group interview was held with experts who began using radioisotopes in medicine in the 1950s and the 1960s. Typical protocols and descriptions of clinical practices of diagnostic radioisotope procedures were defined by the focus group and were used to estimate occupational doses received by personnel, per nuclear medicine procedure, conducted in the 1950s to 1960s using radiopharmaceuticals available at that time. The radionuclide activities in the organs of the reference patient were calculated using the biokinetic models described in ICRP Publication 53. Air kerma rates as a function of distance from a reference patient were calculated by Monte Carlo radiation transport calculations using a hybrid computational phantom. Estimates of occupational doses to nuclear medicine technologists per procedure were found to vary from less than 0.01 μSv (thyroid scan with 1.85 MBq of administered I-iodide) to 0.4 μSv (brain scan with 26 MBq of Hg-chlormerodin). Occupational doses for the same diagnostic procedures starting in the mid-1960s but using Tc were also estimated. The doses estimated in this study show that the introduction of Tc resulted in an increase in occupational doses per procedure.

P194 “PARAOXONASE (PON1) GLN, ARG 192 POLYMORPHISM” AN INDEPENDENT RISK FACTOR FOR CORONARY ARTERY DISEASE IN NORTH-WEST INDIAN POPULATION

The activities of FAD-linked glycerophosphate dehydrogenase (m-GDH), glutamate dehydrogenase (G1DH), glutamate-pyruvate transaminase (GPT) and glutamate-oxalacetate transaminase (GOT) were measured in purified populations of CD3 + lymphocytes from 55 control subjects, 62 type-2 diabetics and 50 non-diabetic relatives of the latter patients. The activity of m-GDH was measured by both a radioisotopic procedure and colourimetric technique. As judged from these measurements and relative to the paired value for G1DH, the incidence of abnormally low m-GDH activity was significantly higher in type-2 diabetics than in control subjects. Moreover, the paired ratio in reaction velocity between the colourimetric and radioisotopic assay of m-GDH was abnormally high in patients with low m-GDH activity. Low m-GDH activity often coincided with increased GPT activity in plasma or high GPTGOT ratio in lymphocytes. No obvious clustering of these anomalies was found in relatives of diabetic patients. These findings suggest that an inherited or acquired genomic defect of m-GDH in lymphocytes, and possibly in pancreatic B-cells, may participate to the pathogenesis of non-insulin-dependent diabetes mellitus.

Long-term monitoring of radiation exposure of employees in the department of nuclear medicine (Szczecin, Poland) in the years 1991-2007

Occupational radiation exposure is a hazard that should be avoided or at least minimised. This study aimed to evaluate the radiation exposure of nuclear medicine department employees monitored during the 1991-2007 period, and to investigate the relationship between the annual effective doses of the personnel and the number of radioisotope procedures performed. Overall, 2014 quarterly effective whole-body doses, categorised into six occupational groups, monitored with personal dosemeters, were analysed statistically. There was a wide variation in the average annual doses among the different occupational groups. During the 17 years covered by this study, there was no incidence of a dose exceeding the annual dose limit of 20 mSv. There was a weak correlation between the average annual dose for monitored employees and the number of nuclear medicine procedures performed. Apart from exposure, personal skill in dealing with radioactive substances, compliance with radiation protection rules is an important factor to minimise the effective dose.

Planar scintimammography and SPECT in neoadjuvant chemo or hormonotherapy response evaluation in locally advanced primary breast cancer

Conventional imaging procedures have proved of limited value in assessing tumor response to neoadjuvant chemotherapy in locally advanced primary breast cancer (LAPBC). We evaluated the usefulness of radioisotopic procedures comparing planar scintimammography (SM) to SPECT, monitoring pre-surgery neoadjuvant chemo- or hormonotherapy response in 32 LAPBC patients. In all cases, 99mTc-tetrofosmin conventional planar SM and SPECT were acquired by dual-head gamma camera with HR parallel hole collimators. In 15 cases, planar SM with small field of view high resolution dedicated breast camera (DBC) was also acquired. Scintigraphic data always correlated with histopathological findings. At surgery, 4/32 patients had pathological complete remission (pCR), while 28/32 patients had residual tumors. Both conventional planar SM and SPECT were true negative in 4/4 (100%) pCR patients, as was DBC in the only studied case. Conventional planar SM and SPECT detected residual tumors in 23/28 (82%) and in 25/28 (89.2%) cases, respectively. Both procedures missed 2 multifocal, scattered microscopic residues, only evidenced at DBC. Conventional planar SM also missed 3 further macroscopic residues (15-20 mm), while SPECT only one of these, a mucinous BC, in which DBC was not performed. DBC correctly classified all other 12 patients in whom the procedure was performed. Both conventional planar SM and SPECT proved useful diagnostic tools in monitoring neoadjuvant chemo/hormono therapy response in LAPBC with SPECT appearing more sensitive; however, our data, although in a limited number of cases, suggest that sensitivity can further be increased using high resolution DBC, especially in detecting microscopic residual tumor foci.

Limited mediastinal lymph node dissection for non-small cell lung cancer according to intraoperative histologic examinations

Although radioisotopic procedures are commonly used to detect sentinel lymph nodes in breast cancer surgery, these procedures are often problematic and not necessarily suitable for lung cancer surgery. Our previous study revealed that the mediastinal sentinel lymph node, defined as the regional mediastinal lymph node, consisted of nodes 2, 3, or 4 in right upper lobe cancers; 3, 7, or 8 in right lower lobe cancers; 4, 5, or 7 in left upper lobe cancers; and 4, 7, or 8 in left lower lobe cancers. On the basis of these findings, we pathologically investigated one representative lymph node at each of the 3 levels dissected during surgical intervention in 69 patients with non-small cell lung cancer from September 1993 through December 2002. Fifty-eight patients with lung cancer underwent lobectomies with limited mediastinal lymph node dissection according to this strategy. Mediastinal lymph node recurrence was observed in only one patient during 41 +/- 25 months (maximum, 98 months) of follow-up. The cancer-specific 5-year survivals were 96.6% in patients with pathologic stage IA disease (n = 31) and 67.4% in patients with stage IB disease (n = 16). These results suggested that limited mediastinal lymph node dissection is applicable to patients with non-small cell lung cancer whose regional mediastinal lymph nodes are not metastatic.

Comparison of radioisotope methods and a non-radioisotope method to measure platelet survival in the baboon

Background: The in vivo survival of autologous fresh and preserved platelets can be measured using 51-Cr and 111-In-oxine radioisotope procedures and by a non-radioisotope procedure using biotin-X-N-hydroxysuccinimide (NHS) with detection in the flow cytometer using fluorescent streptavidin. This study was done to assess the specificity of the radioisotopes 51-Cr and 111-In-oxine and non-radioactive biotin-X-NHS to label platelets to measure their in vivo recovery and lifespan. Study design and methods: In the study reported here, aliquots of autologous platelets from the same baboon were labeled with 51-Cr, 111-In oxine and biotin-X-NHS to measure platelet survival. Both cell-associated and platelet-associated 51-Cr and 111-In oxine radioactivity were assessed to measure the in vivo recovery and lifespan of platelets. Blood volume was measured using the 125I albumin plasma volume and the total body hematocrit. Results: In vivo recovery values measured during the 1–3 h post-infusion period and during the 8 day post-infusion period showed significant differences between the 51-Cr-labeled and the 111-In-oxine labeled platelets. In the 51-Cr-labeled platelets, the cell-associated radioactivity was about 50% higher than the platelet-associated radioactivity. In the 111-In-oxine labeled platelets, the cell-associated radioactivity was about 10% higher than the platelet-associated radioactivity. Similar in vivo recovery values were observed in the biotin-X-NHS labeled platelets and the 111-In-oxine labeled platelets assessed from the cell-associated 111-In-radioactivity. Conclusion: The radioisotope 51-Cr and 111-In are non-specific labels for platelets, whereas biotin-X-NHS is a specific label for platelets identified in the flow cytometer with fluorescent streptavidin. The in vivo recovery values of autologous baboon platelets were similar when assessed from the cell-associated 111-In-oxine radioactivity and biotin-X-NHS labeled platelets.

A low-dose radioisotope procedure for assessment of subcutaneous drug delivery systems used for slow intrathecal infusion of antispasmodic agents.

Retrospective single centre study. To evaluate a low-dose radioisotope imaging procedure for assessment of implanted intrathecal drug delivery and to compare the radiation dose and diagnostic value of these studies with other reported studies using higher administered radiation dose. National Spinal Injuries Centre, Stoke Mandeville Hospital, UK. A total of 11 spinally injured patients with subcutaneous drug delivery systems and uncontrolled spasm were investigated for catheter failure using a low-dose radioisotope procedure with an administered dose of radioactivity of 40 MBq Technetium-99m. Loss of catheter patency was demonstrated in six patients, enabling identification of the site of blockage. Catheter patency and subsequent perfusion of CSF (ie normal result) was demonstrated in five patients. Radiation effective dose was estimated at 1.3 mSv per patient study, with a low associated risk of deleterious effect of one in 13,000. Radioisotope investigation using a reduced administered dose of 40 MBq Technetium-99m DTPA, formulated according to a strict radiopharmaceutical protocol, provides a safe test for assessment of intrathecal drug delivery systems.

Avaliação de foco epileptogênico do lobo temporal: correlação entre SPECT ictal, ressonância magnética e ressonância magnética com espectroscopia de prótons

O objetivo deste trabalho foi determinar a existência de concordância entre os métodos radioisotópico e radiológico e, em caso positivo, avaliar a utilidade do SPECT ictal na determinação do foco epileptogênico. Foram realizados SPECT ictal, ressonância magnética (RM) e ressonância magnética com espectroscopia de prótons (RME) em seis pacientes com epilepsia de lobo temporal refratária. O SPECT ictal foi realizado após a retirada das drogas antiepilépticas durante monitoramento por vídeo-EEG, utilizando-se o 99mTc-ECD, administrado aos pacientes no início da crise. As imagens de RM foram obtidas em T1, T2 e FLAIR, com cortes de 3 e 5 mm de espessura, e a RME foi realizada com técnica PRESS, com voxel único posicionado no hipocampo, bilateralmente. A análise estatística incluiu os valores de Kappa (k), erro-padrão (ep) e o nível de significância (p) para a lateralização do foco. Os achados foram analisados com base na localização por EEG da descarga ictal, no tempo de duração da crise (109-280 s; média: 152 s) e no tempo de administração do traçador (30-262 s; média: 96 s). Obtivemos dados correlatos em quatro pacientes (67%), com valores de k = 0,67, ep = 0,38 e p = 0,041. Concluímos que existe concordância entre SPECT ictal, RM e RME, e a utilidade do procedimento radioisotópico está relacionada aos casos em que o EEG não é diagnóstico e quando há discordância ou indefinição diagnóstica na análise comparativa entre EEG, RM e RME.

D-mannoheptulose phosphorylation by hexokinase isoenzymes.

D-mannoheptulose is a specific inhibitor of D-glucose phosphorylation by hexokinase isoenzymes. In the present study, the phosphorylation of this heptose was investigated by either a spectrophotometric or radioisotopic procedure. Using yeast hexokinase, the phosphorylation of 25 mM D-mannoheptulose only represented 0.02% of that of 5 mM D-glucose. Such a percentage was increased to 3.93% in the case of bovine heart hexokinase. In the latter case, the Km for D-mannoheptulose was close to 0.2 mM and both D-glucose (0.1-1.0 mM) and D-glucose 6-phosphate (also 0.1-1.0 mM) inhibited the phosphorylation of the heptose (0.03-0.60 mM). Human B-cell glucokinase also catalyzed the phosphorylation of D-mannoheptulose (0.1 mM), which was now increased in a bell-shaped manner by D-glucose (1.0-20 mM). Likewise, rat parotid gland, liver and pancreatic islet homogenates catalyzed the phosphorylation of D-[3H]mannoheptulose. The results obtained in these three tissues differed from one another by their absolute values (per mg wet wt.), relative values (by reference to the phosphorylation rate of 10 mM D-glucose), and sensitivity to inhibition by D-glucose (10 mM).

Should nuclear medicine physicians give the results of radioisotope examinations directly to patients?

Patients often ask for the results after a radioisotope procedure, which can make nuclear medicine physicians feel uncomfortable. In Belgium, nuclear medicine physicians are not supposed to disclose results directly to patients, but to send them to the referring physician. We undertook this work to determine the official rules and practical attitudes in other countries. An introductory letter and a questionnaire were sent to 103 eminent nuclear medicine specialists from 37 countries. Seventy responses (32 countries) were received. Official rules seemed to exist in only seven countries. Most of the respondents indicated that their attitude depended on the clinical situation and the results of the test. Many respondents emphasized that, while in some situations the results should be communicated directly to patients in order to initiate treatment rapidly, in other situations, such as cancer, the referring physician was better suited to disclose the results. The advantages and drawbacks of different attitudes are discussed. Practically and universally applicable rules are difficult to establish, but choosing one solution remains preferable to no standardized attitude at all. An official body, including the medical community, representatives of the population and legal experts, should define an official rule which should be widely communicated, stressing its advantages and drawbacks. In practice, all nuclear medicine physicians would have to do would be to stick to the rule.

Localization of the sentinel lymph node in breast cancer by combined lymphoscintigraphy, blue dye and intraoperative gamma probe.

Axillary lymph node status represents the most important prognostic factor in patients with operable breast cancer. A severe limitation of this technique is the relatively high rate of false negative sentinel lymph nodes (>5%). We studied 284 patients suffering from breast cancer; 264 had T1 tumors (16 T1a, 37 T1b and 211 T1c), while 20 had T2 tumors. All patients underwent lymphoscintigraphy 18-h before surgery. At surgery, 0.5 mL of patent blue violet was injected subdermally, and the sentinel lymph node (SN) was searched by gamma probe and by the dye method. The surgically isolated SN was processed for intraoperative and delayed examinations. The SN was successfully identified by the combined radioisotopic procedure and patent blue dye technique in 278/284 cases (97.9%). Analysis of the predictive value of the SN in relation to the status of the axillary lymph nodes was limited to 191 patients undergoing standard axillary dissection irrespective of the SN status. Overall, 63/191 (33%) identified SNs were metastatic, the SN alone being involved in 37/63 (58.7%) patients; a positive axillary status with negative SN was found in 10/73 (13.7%) patients with metastatic involvement. In T1a-T1b patients the SN turned out to be metastatic in 9/53 patients (17.0%). In 7/9 patients the SN was the only site of metastasis, while in 2/9 patients other axillary lymph nodes were found to be metastatic in addition to the SN. None of the 44 patients in whom the SN proved to be non-metastatic showed any metastatic involvement of other axillary lymph nodes. Our results demonstrate a good predictive value of SN biopsy in patients with breast cancer; the predictive value was excellent in those subjects with nodules smaller than 1 cm.

Mapping sentinel lymph node in breast cancer by combined lymphoscintigraphy, blue-dye, and intraoperative gamma-probe.

The purpose of the present work was two-fold: 1) to evaluate the predictive value of the sentinel lymph node (sLN) versus the axillary-node status in patients with T1-T2 breast cancer, and 2) to form an experimental basis for a randomized trial in which one group of patients with non-metastatic sLN will not have axillary dissection. Of a group of 284 patients considered for this analysis, 264 had a T1 cancer (16 T1a, 37 T1b and 211 T1c), while 20 had a T2 cancer; 243 patients were in clinical stage N0 and 41 were N1. All patients underwent lymphoscintigraphy 18 hr before surgery: 10 MBq in 0.15 mL of 99mTc-human albumin nanocolloids (particle size between 50-80 nm) was injected subdermally at the cutaneous projection of the tumor. Static gamma-camera images were acquired every 10-15 minutes until scintigraphic identification of the sLN. At surgery, 1-2 mL of Patent-Blue Violet was injected subdermally, and the sLN was searched by gamma-probe and by the dye method. The surgically isolated sLN was processed for intraoperative Hematoxylin & Eosin (H&E) histology, then for delayed histological and immunohistochemical examinations. The sLN was successfully identified by the combined radioisotopic procedure and Patent-Blue dye technique in 278/284 cases (97.9%). The Patent-Blue dye technique alone identified fewer sLNs than the radioisotopic procedure alone (56.3% versus 97.2%). Analysis of the predictive value of the sLN as to the status of axillary lymph nodes was limited to 197 patients undergoing standard axillary dissection irrespective of the sLN status. Overall, 63/191 (33%) identified sLNs were metastatic, the sLN alone being involved in 37/63 (58.7%) patients; a positive axilla status with negative sLN was found in 10/73 patients with metastatic involvement (13.7% false-negative rate). In conclusion, subdermal lymphoscintigraphy was confirmed to be an effective technique for sLN mapping; the addition of Patent-Blue dye minimally improved intra-surgical identification of the sLN. There was a high, but not absolute, correlation between a negative sLN and a negative axilla.

A survey of close contact regimes between patients undergoing diagnostic radioisotope procedures and children.

When following diagnostic radioisotope procedures, UK legislation requires that we advise patients to avoid close contact with children [1, 2]. How does this advice affect the average nuclear medicine patient? Over a 4 month period, 90 patients in contact with children were asked about their home circumstances, how they coped with avoidance of close contact and the problems caused. On average, the patients were in contact with two children with a mean age of 7 years. Thirty-nine per cent of patients spent < 5 h per day and 30% between 5 and 10 h per day in close contact. However, 13% spent 20-24 h in close contact with children. For most patients (55%), it is easy to avoid close contact, but 25% found it difficult or very difficult. The average in-patient received one visit a day from children of 0.5-1 h duration and 65% of children sat on the patient's bed. Restriction of visits was a problem for 14% of patients. Initially, over one-third of the out-patients felt a medium level of anxiety or higher regarding close contact with children. Given more detailed written information and the opportunity to discuss any queries with a member of staff (70% wished to do so), the proportion fell to less than one-tenth. We found it important to question patients carefully, because home circumstances and levels of close contact cannot be deduced from the age of the child or the relationship between the child and the patient.

FAD-glycerophosphate dehydrogenase activity in lymphocytes of type-2 diabetic patients and their relatives

The activities of FAD-linked glycerophosphate dehydrogenase (m-GDH), glutamate dehydrogenase (G1DH), glutamate-pyruvate transaminase (GPT) and glutamate-oxalacetate transaminase (GOT) were measured in purified populations of CD3 + lymphocytes from 55 control subjects, 62 type-2 diabetics and 50 non-diabetic relatives of the latter patients. The activity of m-GDH was measured by both a radioisotopic procedure and colourimetric technique. As judged from these measurements and relative to the paired value for G1DH, the incidence of abnormally low m-GDH activity was significantly higher in type-2 diabetics than in control subjects. Moreover, the paired ratio in reaction velocity between the colourimetric and radioisotopic assay of m-GDH was abnormally high in patients with low m-GDH activity. Low m-GDH activity often coincided with increased GPT activity in plasma or high GPT GOT ratio in lymphocytes. No obvious clustering of these anomalies was found in relatives of diabetic patients. These findings suggest that an inherited or acquired genomic defect of m-GDH in lymphocytes, and possibly in pancreatic B-cells, may participate to the pathogenesis of non-insulin-dependent diabetes mellitus.

The coupling of metabolic to secretory events in pancreatic islets. Glucose-induced changes in mitochondrial redox state

Mitochondrial NAD +, NADH, NADP + and NADPH were measured in dispersed pancreatic islet cells incubated in the absence or presence of D-glucose and then exposed for 20 s to 0.5 mg/ml digitonin. The latter treatment resulted in the full release of lactate dehydrogenase without any detectable loss of glutamate dehydrogenase. The permeabilized cells were separated from the incubation medium by centrifugation through an oil layer and their content in pyridine nucleotides measured by a radioisotopic procedure coupled to the classical cycling technique. Relative to basal value, D-glucose, in concentrations of 2.8 and 16.7 mM, caused a concentration-related increase in both the NADH/NAD + and NADPH/NADP + ratio. These findings provide the first direct evidence for the induction of a more reduced mitochondrial redox state in glucose-stimulated pancreatic islets.

Hexose metabolism in pancreatic islets: glycogen synthase and glycogen phosphorylase activities.

The activity of glycogen synthase and glycogen phosphorylase was measured in rat pancreatic islet homogenates. For this purpose, the sensitivity of current radioisotopic procedures for the assay of these enzymes in liver extracts was increased by about two orders of magnitude. Even so, the measurement of glycogen synthase and phosphorylase in islet homogenates was hampered by a potent amylase-like activity, resulting in the hydrolysis of preformed or newly formed 14C-labeled glycogen. Acarbose suppressed the latter phenomenon which was found attributable to both minute contamination of isolated islets by acinar cells and genuine alpha-amylase activity in purified islet beta-cells. As measured by the more sensitive method in the presence of acarbose, the a/(a+b) ratio for glycogen synthase activity in islet homogenates was increased in islets preincubated in the presence as distinct from absence of D-glucose and decreased after preincubation with forskolin. These changes represented a mirror image of those evoked by D-glucose and forskolin in the a/(a+b) ratio for glycogen phosphorylase activity. It is concluded that glycogen synthesis and breakdown are regulated in the endocrine pancreas in a manner qualitatively comparable to that prevailing in hepatocytes, the possible participation of an amylase-like activity to glycogen metabolism in intact islet beta-cells requiring further investigation.

Could Non-Insulin-Dependent Diabetes Mellitus Be Attributable to a Deficiency of FAD-Linked Glycerophosphate Dehydrogenase?

In 12 out of 32 non-insulin-dependent diabetic subjects, the activity of FAD-linked glycerophosphate dehydrogenase in T lymphocyte homogenates was abnormally low when measured by both a colorimetric and radioisotopic procedure. A comparable situation characterized by a deficient activity of FAD-linked glycerophosphate dehydrogenase in both the colorimetric and radioisotopic assays was only observed once among 26 other subjects including 11 healthy volunteers, 9 non-diabetic patients, 5 type-1 (insulin-dependent) diabetics, and 1 pancreatectomized diabetic. By analogy, it is speculated that an impaired activity of FAD-linked glycerophosphate dehydrogenase in the insulin-producing pancreatic B-cell could represent a far-from-uncommon contributive factor in the pathogenesis of non-insulin-dependent diabetes mellitus.