Pancreas and islet transplant registry data

From December 16, 1966, to June 30, 1983, some 337 pancreas transplants in 316 diabetic patients from 305 cadaveric and 32 living related donors were performed at 46 institutions throughout the world. A total of 60 pancreas transplants in 56 patients were performed prior to July 1, 1977, with only 2 functioning for more than 1 year. Therefore, the present era includes 277 pancreas trans-plants performed in 262 patients at 39 institutions. Seventy-four of these were done in 1982, while 72 were performed in the first 6 months of 1983 with 11 new institutions reporting. Of the 262 patients in the present era, 74 (28%) have died with 48 (18%) of these dying within the first 3 months of transplantation. Of the 190 pancreas transplants performed up to December, 1982, and available for evaluation of 1-year graft function, 31 (16%) are currently functioning; another 8 (4%) functioned for 1 year but then failed (7) or the recipient died (1). Of the 72 transplants done in the first 6 months of 1983, there are 26 (37%) still functioning. Results are expressed according to technique of handling the ductal drainage, association with kidney transplantation, and association with the type of immunosuppression. Seventeen non-diabetic patients (13 with chronic pancreatitis, 4 with adenocarcinoma) had autotransplantation of a segment of the pancreas after pancreatectomy. Thirteen were said to function but follow-up data are incomplete. There were 73 islet tissue allografts reported as of June 30, 1980, but none of the patients achieved insulin independence. Since then an additional 86 islet tissue allografts have been reported without any insulin independence achieved to make a total of 159 performed without normoglycemia. A total of 79 pancreatectomized patients have received islet tissue autografts with 50% being reported as insulin independent, but the results are difficult to interpret.

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Resumen En el périodo comprendido del 16 de diciembre de 1966 al 30 de junio de 1983, 316 diabéticos han sido sometidos a 337 transplantes pancreáticos (305 cadavéricos y 32 de donantes vivos) en 46 instituciones. En el périodo antes del 1 de julio de 1977 un total de 60 transplantes pancreáticos se ejecutaron en 56 pacientes y solamente 2 funcionaron más de un año. Por consiguiente la actual epoca incluye 277 transplantes pancreáticos ejecutados en 262 pacientes en 39 instituciones. En 1982 se ejecutaron 74 y en los primeros seis meses del 1983 se reportaron 72 nuevos transplantes pancreáticos e incluyó 11 instituciones nuevas. Durante la actual época 74 de 262 pacientes (28%) han muerto y 48 (18%) de estos murieron durante los primeros tres meses del transplante. De los 190 transplantes de páncreas ejecutados hasta diciembre de 1982 y evaluables en relación a su función al año, 31 (16%) estan actualmente funcionando y 8 (4%) funcionaron por un año y fracasaron más tarde (7) o el recipiente murió (1). De los 72 transplantes ejecutados en los primeros 6 meses del 1983, 26 (37%) mantienen buena función. Los resultados son expresados de acuerdo a la tenica utilizada para el drenaje del conducto pancreático, su asociación con transplante renal y el tipo de inmunosupresión utilizado. Diecisiete pacientes no diabéticos recibieron autotransplante de páncreas parcial (13 con pancreatitis crónica y 4 con adenocarcinoma). Trece se han reportado con función, pero la información es incompleta. Hasta el 30 de junio de 1980 se reportaron 73 aloinjertos de tejido de islotes y ninguno logró la insulinoindependencia. Otros 86 injertos de islotes se han reportado desde esa fecha, pero ninguno ha logrado la insulinoindependencia, lo que hace un total de 159 aloinjertos de islotes sin obtener normoglicemia. Setenta y nueve pacientes con autoinjertos de islotes han sido reportado y supuestamente la mitad son insulinoindependientes aunque estos resultados son difïciles de interpretar.

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Résumé Du 16 décembre 1966 au 30 juin 1983, quelque 337 transplantations pancréatiques ont été pratiquées avec des greffons provenant de 305 cadavres et 32 donneurs vivants apparentés, sur 316 patients diabétiques dans 46 établissements à travers le monde. Soixante greffes de pancréas au total ont été faites chez 56 patients avant le 1^er juillet 1977, dont 2 seulement ont fonctionné plus d'un an; c'est pourquoi la revue ci-dessous concerne 277 greffes pratiquées sur 262 malades dans 39 établissements. Soixante-quatorze ont été faites en 1982, tandis que 72 ont été rapportées dans les 6 premiers mois de 1983, dans 11 nouveaux établissements. Sur les 262 patients passés en revue, 74 (28%) sont morts, dont 47 (18%) dans les 3 mois après la greffe. Sur les 190 transplantations pancréatiques réalisées jusqu'à décembre 1982 et pour lesquelles on dispose de résultats de tests pratiqués après un an de fonction du greffon, 31 (16%) sont actuellement fonctionelles et 8 autres (4%) ont échoué après plus d'un an de fonction (7) ou leur receveur est mort(1). Parmi les 72 greffes réalisées dans le premier semestre de 1983, 26 (37%) sont encore fonctionnelles. Les résultats sont classés d'après la méthode de drainage des sécrétions exocrines, l'association ou non à une greffe rénale, et le type de traitement immunosuppresseur associé à la greffe. Dix-sept patients n'étaient pas diabétiques (13 atteints de pancréatite chronique, 4 d'adénocarcinome) mais ont subi une auto-transplantation segmentaire de pancréas; parmi eux, 13 auraient un greffon fonctionnel, mais les données sur l'évolution des sujets sont incomplètes. Soixante-treize hétérogreffes d'îlots ont été rapportées jusqu'au 30 juin 1980, sans qu'une seule entraîne de sevrage définitif de l'insulinothérapie. Depuis lors, 86 hétérogreffes d'îlots ont été rapportées sans entraîner de sevrage insulinique, soit un total de 159 greffes qui ont été pratiquées sans entraîner de retour à la normoglycémie; 79 patients au total ont recu des autogreffes d'îlots et 50% d'entre eux sont décrits comme n'ayant plus besoin d'insuline, mais ces résultats sont difficiles à interprêter.

     

Immunogenetic considerations in islet transplantation: The role of Ia antigens in graft rejection

As demonstrated by Faustman et al., islets that are pretreated with Ia antibodies and complement show markedly prolonged survival as compared with islets, with the same immunogenetic disparity, without antibody pretreatment. In order to test whether it is simply the absence of an allo-Ia disparity that accounts for this finding, we have transplanted islets across class I disparities alone; in certain cases, such islets are rapidly rejected. Yet, even though there is no allo-Ia difference on such islets, pretreatment of the islets with anti-Ia monoclonal antibody also results in markedly prolonged survival. We suggest that the presence of Ia antigens may serve as a differentiation marker for cells that can present class I antigens in an immunogenic manner; further, allo-Ia antigens can lead to a stronger anti-class I rejection response.     

Partial seizures with focal epileptogenic electroencephalographic patterns in three related female patients with fragile-X syndrome

Epilepsy and abnormal electroencephalographic (EEG) patterns have been reported in mentally retarded males with fragile-X syndrome, but the high incidence of epilepsy in such persons has been recognized only recently. These individuals have focal spikes in the EEG similar to the benign rolandic pattern. Female carriers have very rarely been reported to have epilepsy or nonspecific abnormal EEG patterns. We report partial seizures with a focal epileptogenic EEG pattern in two sisters and their grandmother, who are all carriers of fragile-X syndrome. The sisters have mild developmental delay, but the grandmother is of normal intelligence. The mother of the two sisters is known to be a carrier of the fragile-X chromosome and is of normal intelligence, with no history of seizures. It is important for physicians to be aware of the possibility that females presenting with partial seizures of unknown cause may be fragile-X carriers, and enquiry for a family history of intellectual disability should be pursued.     

Clean Intermittent Catheterization in Boys Using the Lofric Catheter

Purpose

We compared a recently developed hydrophilic catheter to the standard polyethylene catheter in regard to hematuria, infection and patient satisfaction.

Materials and Methods

A hydrophilic LoFric^* or standard Mentor^† catheter was assigned at random to 17 and 16 boys, respectively, who were skilled in intermittent self-catheterization. They were evaluated by weekly urinalysis and a questionnaire.

Results

Significantly fewer episodes of microscopic hematuria occurred in the LoFric than Mentor catheter group (9 episodes in 6 subjects versus 19 episodes in 11, p less than 0.05). There were also fewer episodes of bacteriuria in the LoFric group but the difference was not statistically significant. Mean scores plus or minus standard deviation on a visual analogue scale with 0 equal to most and 10 equal to least favorable were LoFric 3.3 plus/minus 2.8 versus Mentor 4.9 plus/minus 2.7 for catheter convenience and 2.7 plus/minus 2.4 versus 4.2 plus/minus 2.6 for insertion comfort, significantly favoring the LoFric group (p less than 0.05 for both). Of the 16 LoFric subjects 13 preferred to continue its use, particularly those with a history of urethral trauma or sphincteric spasm.

Conclusions

In boys the LoFric catheter appears to cause less trauma. Although it is not reusable and is more expensive than the standard catheter, satisfaction is higher with the LoFric device and for select patients it has significant advantages.     

Cell proliferation kinetics of MCF-7 human mammary carcinoma cells in culture and effects of tamoxifen on exponentially growing and plateau-phase cells

MCF-7 human mammary carcinoma cells were inoculated into 150-sq cm flasks at 3 X 10(5) cells/flask, and after a lag period of about 48 hr, these cells grew exponentially for 5 days with a mean population doubling time of about 24 hr. During exponential growth, 80 to 90% of cells were in the "rapidly cycling" pool, the clonogenic fraction was 50 to 60%, and the mean percentage of cells in the G0-G1, S, and G2 + M phases of the cell cycle was 48.9 +/- 0.6% (S.E.), 39.4 +/- 0.6%, and 11.6 +/- 0.3%, respectively. These parameters changed rapidly between Days 7 and 13 when plateau phase was reached. Between Days 13 and 18, 74.8 +/- 0.7% of cells were in G0-G1, 15.3 +/- 0.4% were in S, and 9.8 +/- 0.6% were in G2 + M phase. Only about 30% of these cells were cycling rapidly, and the clonogenic fraction had fallen to less than 10%. Tamoxifen induced a dose-dependent decrease in the growth rate of exponentially growing cells, which was accompanied by a dose-dependent increase in percentage of G0-G1-phase cells, and a decline in percentage of S-phase cells. At doses greater than or equal to 10 microM, a 24-hr pulse of tamoxifen was cytotoxic to exponentially growing cells. Plateau-phase cells were less sensitive to these effects of tamoxifen. In an attempt to define the kinetic basis of the G0-G1 accumulation induced by tamoxifen, asynchronous MCF-7 cells were pretreated for 42 hr with various doses of tamoxifen, and the rate of efflux of cells from the G0-G1 phase of the cell cycle was assessed by blocking their reentry into G1 with ICRF 159. Following treatment of control cultures with ICRF 159, two populations of cells were distinguished by their rates of efflux from G0-G1 phase. The majority of cells left G0-G1 rapidly with a mean t1/2 of 2.3 hr ("rapidly cycling" cells). However, about 18% of cells had a much slower rate of exit with a mean t1/2 of about 30 hr ("slowly cycling" cells). Pretreatment with tamoxifen resulted in a dose-dependent decrease in the proportion of rapidly cycling cells and an increase in the proportion of cells with slow G1 transit times. Although this appeared to be the predominant effect, tamoxifen also decreased the rate at which the slowly cycling cells traversed G1. Simultaneous treatment with estradiol returned these parameters to control values at doses of tamoxifen less than or equal to 5 microM, partially reversed the effect of 7.5 microM tamoxifen, but was without effect on the arrest of cell cycle progression induced by 10 microM tamoxifen. It is concluded that cells accumulate in G0-G1 following tamoxifen treatment due to an increase in the proportion of slowly cycling cells at the expense of a population of rapidly cycling cells, which appear to be relatively uninfluenced by the drug.     

The ranges of insulin response and glucose tolerance in lean, normal, and obese women during pregnancy.

OBJECTIVE: We characterized insulin secretion and glucose disposal in a large unselected group of women, encompassing the full spectrum of glucose tolerance in pregnancy, and related the findings to maternal obesity. STUDY DESIGN: Intravenous glucose tolerance and first-phase insulin response were measured at about 32 weeks' gestation in 690 unselected pregnancies. The women were designated as "lean," "normal," or "obese" on weight-for-height criteria. RESULTS: The distribution of insulin response was bimodal, but there was no corresponding dichotomy in maternal glucose disposal rate. Insulin response was greatest and glucose disposal rate slowest in obese women. In general, "poor" glucose tolerance was associated with relatively low insulin output. It was not possible to identify any cluster of women, obese or otherwise, in whom poor glucose tolerance was specifically associated with an unusually high insulin response. CONCLUSION: The data indicate that the distribution of glucose tolerance in pregnancy is a continuum. Glucose intolerance represents one end of that spectrum and is attributable to insufficient insulin secretion. This relative insufficiency is most frequent with maternal obesity.     

Effect of nonmedical factors on family physicians' decisions about referral for consultation.

OBJECTIVES: To identify nonmedical factors perceived by family physicians (FPs) and consultants as important influences on decisions about referral for consultation, to determine the relative frequency with which such factors are cited and to identify those factors ranked as most important by the FPs and consultants. DESIGN: Survey with semistructured interview between July 1989 and April 1990. PARTICIPANTS: A total of 41 FPs and 20 consultants who were practising or had practised previously in Nova Scotia. INTERVENTIONS: The questionnaire comprised 10 questions: 4 were nondirective "probes" designed to elicit responses without suggesting possible answers, 2 asked the participants to rank such responses in order of importance, and 4 were "prompts" that asked for comments about a list of factors based on a review of the literature. RESULTS: A total of 4845 discrete items were mentioned as being capable of influencing FPs' decisions about referral for consultation. Aggregation of related items resulted in a list of 35 nonmedical factors, of which 11 were identified by at least half the respondents and 14 by less than half but more than 10. These 25 factors fell into three categories: patient and family factors (e.g., patient's wishes), FP and consultant factors (e.g., FP's capabilities), and other influences (e.g., style of practice). On the basis of both frequency of identification and priority scores "patient's wishes" emerged as the most important factor. Two medical factors that were consistently cited--type of problem and age of patient--were thought to interact with the other factors. CONCLUSION: Certain nonmedical considerations may substantially affect physicians' referral practices.