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Biomedical subjects

J L Larsen

Publications and source records attributed to J L Larsen.

At least 109 records · Page 6Linked to original sources

Cholelithiasis in pancreas and kidney transplant recipients with diabetes.

BACKGROUND: Vascularized pancreas transplantation (PTx) for type I diabetes mellitus results in euglycemia at the expense of chronic immunosuppression, hyperinsulinemia, and dyslipidemia. However, the effect of PTx on native biliary lithogenesis remains unknown. METHODS: To address this issue, we retrospectively studied 72 consecutive pancreas transplant recipients and compared them with patients both with (n = 35) and without (n = 52) diabetes mellitus undergoing kidney transplantation alone (KTA). All patients underwent pretransplantation abdominal ultrasonography, which was repeated at 6- to 12-month intervals after transplantation. PTx recipients were managed with quadruple immunosuppression with OKT3 induction. Kidney transplant recipients received cyclosporine and prednisone. RESULTS: Seventeen (30.4%) of 56 evaluable PTx recipients had gallstones at a mean interval of 13 months (range, 5 to 24) after PTx. Eleven patients underwent open cholecystectomy (with one surgical exploration of common bile duct for choledocholithiasis), three underwent laparoscopic cholecystectomy, and the other three are being managed expectantly. Gallstone analysis revealed predominantly cholesterol stones. The incidence of cholelithiasis in kidney transplant recipients with and without diabetes mellitus was 27.3% and 12.2%, respectively (p = 0.04). CONCLUSIONS: Pancreas transplant and kidney transplant recipients with diabetes are predisposed to the development of gallstones compared with recipients without diabetes. An interaction between diabetes mellitus-induced gallbladder dysmotility and cyclosporine-induced cholestasis may be a possible mechanism. We recommend serial ultrasonographic examinations in pancreas transplant and kidney transplant recipients, and cholecystectomy in pancreas transplant recipients with cholelithiasis should be considered.

Adult↗

Human growth hormone enhances pertussis toxin-stimulated ADP-ribosylation of Gi in Nb2 cell membrane.

The Nb2 node lymphoma cell line has been widely used as a model for investigating lactogen cellular actions. Both pertussis (PTX) and cholera (CTX) toxins modulate lactogen-stimulated Nb2 cell mitogenesis, suggesting G protein involvement in lactogen signal transduction. The following studies were performed to further investigate this possibility. Both PTX-sensitive (41 kDa) and CTX-sensitive substrates (42 and 45 kDa) were identified in Nb2 cell membrane and recognized by specific anti-Gi and anti-Gs antibodies, respectively. Equal numbers of Nb2 cells were then incubated with the lactogen human growth hormone (hGH, 10 ng/ml) for 0-72 h. Membrane protein prepared from each time point (50 micrograms) was compared in toxin-stimulated ADP-ribosylation studies. CTX-stimulated ADP-ribosylation was unaffected by prior hGH incubation. PTX-stimulated ADP-ribosylation increased 237 +/- 69% (X +/- S.E.) compared with 0-h controls (n = 11; p less than 0.01) after 4-7 h of hGH incubation then decreased toward 0-h samples by 24 and 72 h. No change in Gi alpha concentration was observed, but beta subunit concentration increased (145 +/- 14% at 7 h; p less than 0.01; n = 3) in a time course that paralleled the changes in PTX-stimulated ADP-ribosylation. In summary, 1) both Gi and Gs were present in Nb2 cell membrane, 2) incubation of cells with a lactogen, hGH, for 4-7 h markedly enhanced PTX-stimulated ADP-ribosylation of Gi alpha in vitro, whereas CTX-stimulated ADP-ribosylation of Gs alpha was unchanged, and 3) although no change in Gi alpha concentration was observed, beta subunit concentration increased in parallel with the increase in PTX-stimulated ADP-ribosylation of Gi alpha. These results suggest that hGH may modify PTX-stimulated ADP-ribosylation of Gi not by changing Gi alpha concentration, perhaps by increasing beta subunit concentration, enhancing association of Gi alpha by beta gamma subunits, which, in turn, is preferentially ADP-ribosylated. This may represent a late signal transduction event and may also have implications for other effectors dependent on Gi-mediated events.

Adenosine Diphosphate Ribose↗

Lipid status after combined pancreas-kidney transplantation and kidney transplantation alone in type I diabetes mellitus.

This study was designed to compare changes in lipid status following organ transplantation between type I diabetes mellitus (DM-I) patients receiving combined pancreas-kidney transplantation (PKT) with those receiving kidney transplantation alone (KTA). A retrospective chart review was used to identify pre- and posttransplantation fasting total cholesterol (TC) and triglycerides (TG) in three groups: DM-I patients receiving KTA (DM:KTA; n = 14), DM-I patients receiving PKT (DM:PKT; n = 20), and kidney transplant recipients without DM (NDM; n = 16). The groups were matched for age, gender, weight, duration of dialysis, smoking history, and duration of diabetes mellitus. Linear regression was used to analyze differences in lipid trends over time (up to 24 months posttransplantation) and the effects of prednisone dose, cyclosporine dose, and serum creatinine. Preoperative TC was significantly lower in the DM:KTA group (P < 0.05) compared with DM:PKT or NDM. There were no significant differences in preoperative TG between the three groups. TC and TG decreased over time only in DM:PKT (P = 0.0112, P = 0.0278, respectively). TC increased and TG was unchanged over time in DM:KTA (P = 0.0003, P = 0.1103, respectively). Neither TC nor TG changed over time in NDM. Trends of TC and TG for DM:PKT were significantly different from DM:KTA (P < 0.01 for both). Trend of TC for NDM was also significantly different from DM:PKT (P = 0.0061). Prednisone dose was significantly related to TC in DM:KTA and NDM (P < 0.01) while cyclosporine dose was significantly related to TC for DM:KTA only (P = 0.0013) in the presence of time. None of the variables tested (prednisone dose, cyclosporine dose, and serum creatinine) significantly affected TG in the presence of time. In summary, TC and TG decreased over time only in DM:PKT. In contrast, TC increased while TG was unchanged in DM:KTA over the same interval (0-24 months). If these trends continue, the beneficial change in lipids in the DM:PKT group may translate into a net improvement in atherosclerosis-mediated events for diabetic patients with chronic renal failure who receive PKT compared with those who do not.

Adult↗

Lipid status after pancreas-kidney transplantation.

OBJECTIVE: This study was performed to determine the net effects of euglycemia, resolution of renal failure, immunosuppressant drugs, and hyperinsulinemia on fasting lipid profiles of patients with renal failure and insulin-dependent diabetes mellitus (IDDM) after combined pancreas-kidney transplantation (PKT). RESEARCH DESIGN AND METHODS: Thirty subjects with IDDM received PKT between April 1989 and October 1990, and all were studied. Mean +/- SE age was 35.2 +/- 1.3 yr; 19 recipients were men, and 11 were women. All had a functioning pancreatic allograft post-PKT. Fasting lipid profiles including total cholesterol (C), triglyceride (TG), high-density lipoprotein cholesterol (HDL-chol), and C/HDL-chol were compared before and after PKT (38-555 days divided into groups: preoperation and 0-2, 3-8, and 9-19 mo). RESULTS: Significant hyperlipidemia was observed preoperatively (means +/- SE): C, 5.92 +/- 0.27 mM; HDL-chol, 1.07 +/- 0.09 mM; TG, 5.85 +/- 0.56 mM; and C/HDL-chol, 6.49 +/- 0.83. All lipids and C/HDL-chol dropped immediately after PKT (0-2 mo vs. preoperation, all P less than 0.01, except HDL-chol). After this immediate postoperative period, C, HDL-chol, and TG stabilized at new concentrations. C (5.44 +/- 0.22 mM) and TG (4.54 +/- 0.48 mM) levels were less than preoperation (not statistically significant and P less than 0.05, respectively). HDL-chol was greater than preoperative values (1.29 +/- 0.06 mM, P less than 0.05). C/HDL-chol dropped after PKT (0-2 mo, 4.85 +/- 0.18, P less than 0.01) and continued to decrease throughout the observation period (3-8 mo, 4.42 +/- 0.23; 9-19 mo, 4.23 +/- 0.23; both P less than 0.01 vs. preoperation). There was no statistical difference between lipid concentrations in male and female subjects. CONCLUSIONS: The lipid status of subjects with IDDM and renal failure was abnormal before PKT and once lipid concentrations stabilized after PKT (greater than 2 mo), HDL-chol was higher and TG and C/HDL-chol levels were significantly lower than preoperative values. If these changes are sustained, risk of future cardiovascular disease in this group of patients might be significantly reduced.

Adult↗

Cyclic guanosine monophosphate analogs do not reverse bacterial toxin modulation of lactogen-stimulated NB2 cell mitogenesis.

Pertussis toxin (PT) and cholera toxin (CT) have been shown to modulate lactogenic hormone-stimulated Nb2 cell mitogenesis, a lactogen-dependent cell line. As both toxins have been shown to alter guanylate cyclase activity in other cell systems, cyclic guanosine monophosphate (cGMP) analogs, 8-bromo or dibutyryl cGMP, were added to determine if they could reverse the toxin-mediated effects. In the absence of bacterial toxins, both cGMP analogs enhanced lactogen-stimulated Nb2 cell mitogenesis in a multiphasic pattern. At maximal enhancement, the effect was statistically significant but not marked (113 +/- 5%; p less than 0.01). Neither cGMP analog increased lactogenic binding site number or affinity so cGMP must affect lactogen action following receptor binding. Neither analog could stimulation Nb2 cell mitogenesis in the absence of lactogens so cGMP is not a second messenger for lactogens in this cell system. Finally, neither cGMP analog reversed the inhibitory effects of either bacterial toxin on lactogen-stimulated Nb2 cell proliferation. In summary, although bacterial toxins may be capable of altering guanylate cyclase activity, as addition of cGMP analogs do not reverse toxin-mediated effects on lactogen-stimulated mitogenesis, these toxins' actions must be mediated predominantly through other mechanisms that may have significant importance to lactogen signal transduction.

Animals↗

[Laryngocele].

We report the cases of five patients with laryngocele. In every case the diagnosis was made by computerized tomography. The laryngocele was internal in two cases, external in one case and combined in the rest. One of the patients had bilateral laryngoceles. The value of CT in the diagnosis is stressed, and it is recommended that this radiologic examination (or MRI) should be performed in patients with otherwise unexplained long-standing hoarseness and attacks of stridorous respiration.

Aged↗

Occurrence of plasmids in Danish isolates of Vibrio anguillarum serovars O1 and O2 and association of plasmids with phenotypic characteristics.

Two hundred and twenty-eight isolates of Vibrio anguillarum serovar O1 (125 isolates) and serovar O2 (103 isolates) have been characterized with regard to plasmid contents, biochemical properties, and in vitro hemagglutination and hydrophobic properties. Among 74 V. anguillarum isolates from diseased fish, 63 carried only a 67-kb plasmid (pJM1), 9 carried an additional 98-kb plasmid, and 1 isolate carried only the 98-kb plasmid. Only one isolate was without plasmids. In V. anguillarum serovar O1 from nondiseased fish (mucus and gills), plasmids of the same sizes were present in 29 isolates (58%), whereas 21 isolates (42%) were plasmid free. Based on hemagglutination and biochemical properties, V. anguillarum serovar O1 isolates were divided into eight biovars. The plasmid-carrying strains (102 isolates) all fell within biovars 1 and 2, whereas the 23 strains of biovars 3 to 8 were without plasmids. It was tentatively concluded there are two populations of V. anguillarum serovar O1. One population contains plasmid(s), is hemagglutination negative and trehalose negative, and does not form pellicles in broth cultures, whereas the other population is plasmid free and has the opposite characteristics. The former group is the one related to disease in fish. All 20 V. anguillarum serovar O2 isolates from the environment were without plasmids, whereas 54 (65%) of the isolates from fish (trout and cod) carried plasmids. The biochemical diversity within serovar O2 was pronounced; 13 different biovars were demonstrated. No correlation between the presence of plasmids and biochemical properties was observed.

DNA, Bacterial↗

Characterization of Vibrio anguillarum and closely related species isolated from farmed fish in Norway.

A total of 264 bacterial strains tentatively or definitely classified as Vibrio anguillarum were examined. The strains were isolated from diseased or healthy Norwegian fish after routine autopsy. With the exception of five isolates from wild saithe (Pollachius virens), the strains originated from nine different species of farmed fish. The bacteria were subjected to morphological, physiological, and biochemical studies, numerical taxonomical analyses, serotyping by slide agglutination and enzyme-linked immunosorbent assay, DNA-plasmid profiling, and in vitro antimicrobial drug susceptibility testing. The results of the microbiological studies were correlated to anamnestic information. The bacterial strains were identified as V. anguillarum serovar O1 (n = 132), serovar O2 (n = 89), serovar O4 (n = 2), serovar O8 (n = 1), and not typeable (n = 1) as well as Vibrio splendidus biovar I (n = 36) and biovar II (n = 1), Vibrio tubiashii (n = 1), and Vibrio fischerii (n = 1). V. anguillarum serovar O1 or O2 was isolated in 176 out of 179 cases of clinical vibriosis in Atlantic salmon (Salmo salar). V. anguillarum serovar O1 was the only serovar isolated from salmonid fish species other than Atlantic salmon, while V. anguillarum serovar O2 was isolated from all marine fish suffering from vibriosis. A 48-Mda plasmid was isolated from all V. anguillarum serovar O1 isolates examined. Serovar O2 isolates did not harbor any plasmids. Resistance against commonly used antibiotic compounds was not demonstrated among V. anguillarum isolates. Neither V. splendidus biovar I nor other V. anguillarum-related species appeared to be of clinical importance among salmonid fish.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Combined pancreas--kidney transplantation in Nebraska.

UNLABELLED: In the last 2 years, we have performed combined pancreas-kidney transplantation in 38 Type I diabetics with nephropathy. The mean age of the recipient group was 35 years (range 24-51) with a mean duration of diabetes of 22 years (range 13-41). All patients received quadruple immunosuppression with OKT3 induction. All patients are normoglycemic and insulin independent with a mean glycosylated hemoglobin level of 5.2 +/- 1.1% and a mean serum creatinine of 1.9 +/- 0.5 mg/dl. Metabolic effects of pancreas transplantation included fasting hyperinsulinemia and hyperglucagonemia with exaggerated insulin and glucagon responses to glucose and arginine, respectively, that improved slightly with time. Patient and kidney graft survival are 100% and pancreas graft survival is 94.7% after a mean follow-up interval of 15 months. CONCLUSION: Combined pancreas-kidney transplantation is the treatment of choice for selected Type I diabetics with nephropathy and results in euglycemia despite immunosuppression.

Adult↗

Radiographic anatomy of the distal dural sac. A myelographic investigation of dimensions and termination.

A radio-anatomical study was performed of the distal dural sac (DS) in 121 patients subjected to myelography. In 83.4% the termination of the DS was located from the upper half of the S1-segment to the lower half of the S2-segment. In the remaining patients the dural terminations were more distally located. The average location of the DS-termination was higher than that found in a previous anatomic study. The inference is that in patients with low-back pain and sciatica, the DS tends to terminate at a higher spinal level than in a non-selected anatomic material. The caudal reduction in sagittal diameter of the DS was less than that of the frontal diameter of the sac. The linear diminution in cross-sectional area of the DS from the level of L3 towards the lumbo-sacral junction was not correlated with the degree of caudal extension of the DS into the sacrum. Thus the length of the DS and its transverse diameters are independent of each other. These results supported the view that the location of the termination of the DS (and hence that of the spinal cord) is not related to stenosis of the central spinal canal.

Adolescent↗

Combined pancreas-kidney transplantation: preliminary results and metabolic effects.

UNLABELLED: Vascularized pancreas transplantation (PT) results in a self-regulating endogenous source of insulin. In the last 18 months, we have performed combined pancreas-kidney transplantation in 25 type I diabetics with nephropathy. The mean age of the recipient group was 35 yr (range 24-51) with a mean duration of diabetes of 22 yr (range 13-41). All patients received quadruple immunosuppression with OKT3 induction. All patients remained normoglycemic and insulin independent with a mean glycosylated hemoglobin level of 6.0 +/- 1.1% and a mean serum creatinine of 1.7 +/- 0.5 mg/dl. Metabolic control and hormonal profiles were assessed by intravenous glucose challenge followed by arginine stimulation. Metabolic effects of PT included fasting hyperinsulinemia and hyperglucagonemia with exaggerated insulin and glucagon responses to glucose and arginine, respectively. Patient and graft survival is 100% after a mean follow-up interval of 8 months. CONCLUSION: combined pancreas-kidney transplantation is a valid treatment option for diabetic nephropathy, and results in near-complete normalization of glucose metabolism.

Actuarial Analysis↗

Two equally valid interpretations of the linear multicompartment mammillary pharmacokinetic model.

In pharmacokinetic modeling it is common to use compartmental structures to describe the disposition of a drug in the blood or plasma. Typically, a linear multicompartment mammillary model is equated with the multiexponential equation derived from observing the decay of the plasma drug concentration following an intravascular injection. Classically, the mammillary models are constructed so that the concentrations in each of the compartments are equal at steady state, the apparent volume of distribution at steady state is equal to the sum of the individual compartment volumes, and the apparent volume of each peripheral compartment is equal to the ratio of its intercompartmental rate constants times the central compartment volume. On the basis of what can be measured in the plasma, however, it is equally valid to assume that the sizes of the peripheral compartment volumes are equal to the central compartment volume and that the steady-state concentration in each peripheral compartment is equal to the ratio of its intercompartmental rate constants times the concentration in the central compartment. In fact, these are but two of an infinite number of interpretations of the peripheral compartment volumes.

Infusions, Intravenous↗

Dynamic aspects of expanding cava septi pellucidi et Vergae.

Two paediatric patients with expanding cysts of the cava Vergae et septi pellucidi are presented. In the first patient, consecutive CT scans showed a growing cavum thought to be responsible for his dramatic increase in head circumference. In the other patient, the expanding cavum was discovered because a routine skull X-ray after minor head trauma revealed marked impressiones digitatae. Both patients were successfully treated with stereotactically placed internal shunts from the cysts via the lateral ventricle to the subarachnoid space. During this procedure, contrast medium was instilled, and the cysts were visualized on postoperative CT scans. Some dynamic aspects of such expanding cava are discussed.

Brain Diseases↗

Prolactin inhibition of pregnant mare's serum stimulated follicle development in the rat ovary.

Prolactin (PRL) effects on the female reproductive system have been presumed to occur primarily at the hypothalamic-pituitary level. The following studies were designed to evaluate whether PRL can directly alter gonadotropin actions at the ovarian level. In the first experiment, 10 groups of 7 cycling adult female rats were given a daily dose of pregnant mare's serum (PMS: 25 IU) and either saline (SAL) or PRL (0.25, 0.8, 2.5, 8, or 25 micrograms) twice daily for 4 days. In the second experiment, PMS (6 doses: 0-75 IU/d; 16 animals/dose) was administered to all animals while half the animals at each PMS dose received PRL (25 micrograms twice daily) and half received an equal volume of diluent. Finally, hypophysectomized (hypox) adult rats (n = 5-6/group) received 25 IU PMS/d and PRL (0-75 micrograms) twice daily. An additional group received 0 PRL and 0 PMS. Ovarian weight and histology were evaluated at the completion of each study. In the first experiment, PRL inhibited PMS-stimulated ovarian weight gain in a dose-dependent manner (p less than 0.01). Numbers of preantral (p less than 0.005) and antral (p less than 0.05) follicles were decreased in animals receiving an inhibitory dose of PRL (25 micrograms BID) compared to controls. In the second experiment PRL (25 micrograms BID) again inhibited PMS-stimulated ovarian weight (p less than 0.01) at all doses of PMS. Finally, in hypox animals, PRL inhibited PMS-stimulated ovarian weight gain (25 and 75 micrograms PRL: p = 0.001), and mean number (p less than 0.001) and diameter (p less than 0.001) of antral ovarian follicles (8-75 micrograms PRL) compared to controls. In summary, administration of PRL inhibited PMS-stimulated ovarian weight gain, and antral follicle diameter (in hypox animals only) and number in adult female rats suggesting that in states of hyperprolactinemia, PRL alters gonadotropin-mediated activities (i.e., folliculogenesis) directly at the ovarian level in addition to its hypothalamic and pituitary actions.

Analysis of Variance↗

Restriction fragment length polymorphism of the Vibrio anguillarum serovar O1 virulence plasmid.

Seventy-eight strains of Vibrio anguillarum serovar O1, all harboring one 65- to 70-kilobase plasmid, were typed according to restriction fragment length polymorphism of the plasmid. Six types, three of which comprised 96% of the strains examined, were produced with the restriction endonuclease BamHI. The fragment length polymorphism type did not correlate to any of 12 different phenotypic properties tested.

Bacterial Typing Techniques↗

[The risk of infection from the sea: Vibrionaceae].

Infections caused by marine vibrios appear to be an increasing problem. Gastroenteritis, soft tissue-infection and septicaemia are the most prevalent manifestations. Different environmental and traditional water quality measurements do not indicate the risk. These infections are confined to the summer and late summer with water temperatures exceeding 20 degrees C. Tourists may be exposed to an extraordinary risk, and infections may not become apparent until they have returned home. High risk groups (e.g. immunocompromized) have a high case-fatality rate. The extremely rapid onset of these infections demand aggressive antibiotic therapy and vigorous debridement at an early stage. Gastrointestinal disorders may necessitate fluid replacement and tetracycline is recommended in severe cases.

Denmark↗