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Biomedical subjects

J L Larsen

Publications and source records attributed to J L Larsen.

At least 91 records · Page 5Linked to original sources

Pancreas transplantation for type I diabetes mellitus. Do the benefits offset the risks and cost?

Combined pancreas-kidney transplantation is becoming increasingly acceptable as the preferred procedure for selected patients with insulin-dependent (type I) diabetes who are being considered for kidney transplantation. This is because the combined procedure has the added benefit of superior glycemic control and improved quality of life with greater potential for rehabilitation. Neither patient mortality nor kidney-graft survival is significantly altered by adding a pancreas to a kidney transplantation. However, overall morbidity after the combined operation is greater than that after kidney transplantation alone. This increase in morbidity and the higher total cost must be balanced against the extra benefits to the patient. These benefits include (1) attainment of normal glucose concentrations without the use of exogenous insulin and despite the use of corticosteroids, (2) greater improvement in lipid profiles, and (3) heightened quality of life. It is hoped that continued advances in immunosuppressive strategies and diagnostic technology will enhance the already good results achieved with pancreas transplantation. Other strategies for treatment of type I diabetes are being actively investigated, including islet-cell and fetal pancreas transplants, gene therapy, implanted insulin pumps, and artificial pancreas units. Although any or all of these methods may have a role in the treatment of diabetes mellitus in the future, it will be difficult for any technique to improve on the quality of glucose metabolism already achieved by vascularized pancreas transplantation.

Combined Modality Therapy↗

Elevated cerebrospinal fluid proteins in sciatica caused by disc herniation.

We carried out a study of cerebrospinal fluid (CSF) proteins in 180 patients with sciatica caused by lumbar disc herniation to elucidate further the degree and mechanisms of protein elevations. The 63 controls were patients with tension headache or migraine without aura. The CSF/serum albumin ratios were higher in the patients (mean 8.84, SD 5.16) than in the controls (mean 5.60, SD 2.33). Similar differences were found for the CSF/serum IgG ratios and the CSF-total proteins. The CSF/serum albumin ratios, CSF/serum IgG ratios and the CSF-total protein concentrations were higher in men than in women among the patients. We suggest that the significant difference in ratio parameters between patients and controls indicates a leak of plasma albumin, most likely IgG, into the CSF in patients with sciatica. The leak was more pronounced in men. Also in the control group the CSF/serum albumin and CSF/serum IgG ratios were higher in men.

Adolescent↗

Gender differences in lipid alterations following combined pancreas-kidney transplantation.

We have previously demonstrated that the lipid profile improves following successful combined pancreas-kidney transplantation (PKT). In this study, we examined whether changes in the lipid profile were different in men than in women following PKT. Fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and the TC to HDL ratio (TC/HDL) were evaluated in 47 patients (27 men and 20 women) with normal graft function following PKT. Lipids were evaluated at regular intervals 3.5 months to 2.2 years post-PKT (a total of 317 observations). After PKT, TC/HDL decreased (P < .05), TC was unchanged, and HDL increased (P < .05) in both men and women. Although TG decreased in both men and women, it reached statistical significance in men only (P < .05). There were no significant differences in any lipid parameters between men and women before PKT, but after PKT, TC, TG, and HDL were higher in women (240 +/- 11, 183 +/- 17, and 64 +/- 19 mg/dL, respectively) than in men (207 +/- 6, 143 +/- 11, and 53 +/- 2 mg/dL, P < .05 for each). When post-PKT values were analyzed for trends over time, both TC and TG decreased (P < .05 for both) without any significant difference in trends between men and women. When six individuals who had received lovastatin at any time during their postoperative course were removed from analysis, the gender differences in TG post-PKT and the decrease in TG over time were no longer statistically significant (P > .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Cerebrospinal fluid protein concentrations related to clinical findings in patients with sciatica caused by disk herniation.

The protein concentration in the cerebrospinal fluid (CSF) is often increased in patients with sciatica, probably due to leaking of plasma proteins through the blood-nerve root barrier into CSF. Positive straight leg raising test, paresis, altered sensibility, reduced reflexes, and type of treatment were related to the CSF protein concentrations in 180 patients with sciatica caused by verified lumbar disk herniation. Significantly higher values of the CSF/serum albumin ratio and the CSF/serum immunoglobulin G ratio were found both in patients with positive straight leg raising test results and paresis compared with patients with no clinical findings. In the patients who had undergone emergency surgery, the same ratio parameters were significantly higher when compared with those who had undergone routine surgery and those had not undergone surgery. Elevated CSF proteins seem to be important indicators of the functional status of the nerve root and a measure of the degree of seriousness of sciatica. The interaction of smoking on CSF proteins was also studied.

Adult↗

Characterization of Aeromonas salmonicida subsp. salmonicida: a comparative study of strains of different geographic origin.

A total of 130 strains of the fish pathogen Aeromonas salmonicida isolated in Denmark, Norway, Scotland, Canada and the USA were examined. The strains originated from farmed salmonid fish. The biochemical, physiological and serological characteristics, antibiotic resistance patterns and cell surface-related properties were compared. Aeromonas salmonicida was found to be remarkably consistent in general cultural and biochemical characteristics. It is noteworthy that the strains were positive in the fermentation of L-arabinose and were negative in the fermentation of D-arabinose. All the strains were highly proteolytic. It was observed, however, that 5% of the strains did not digest calf and trout serum and the production of haemolysin and degradation of casein by the same strains were delayed compared with the other strains. Common to all of the rough strains were auto-aggregation and ability to bind the dyes Coomassie brilliant blue and Congo red and the majority of these strains were highly hydrophobic. The strains were tested for their susceptibility to 22 antibacterial agents. Antibiotic resistance profiles of Aer. salmonicida indicated that resistance to the quinolones and oxytetracycline was increasing and that multi-resistant strains were found in several countries. The variation found in antibiograms could have potential as epidemiological markers in certain geographic areas.

Aeromonas↗

Sequelae one year after meningococcal disease.

Of 99 consecutive patients with meningococcal disease, 6 died during the acute stage. The 93 survivors were examined one year after hospitalization. 21 (40%) of the adults and 6 (15%) of the children had definite sequelae, and an additional 27% and 11% possible sequelae. 6 adults (12%) and 1 child (2%) had definite neurological sequelae. Electroencephalography (EEG) abnormalities were observed in 7 adults (14%) and 2 children (5%). Epileptogenic activity was present in 3 of these, but none had experienced seizures. 8 adults (19%) and 5 children (14%) had sensorineural hearing loss or impaired vestibular function. Cerebral computerized tomography (CT) scan showed definite and possible abnormalities in 1 (3%) and 6 (18%), respectively, of the 34 patients tested. Neuropsychological tests were performed in 9 patients, 2 of these showed definite impairment. The frequency of neurological abnormalities was higher than in many previous studies, probably reflecting the more comprehensive examinations performed in the present study. However, only 3 patients had serious sequelae. The results suggest that the occurrence of sequelae after meningococcal disease is related to the severity of the acute disease. This may explain the higher rate of sequelae in adults, who have a higher proportion of seriously ill patients. The presence of meningitis is not required for the occurrence of neurological sequelae.

Adolescent↗

Anti-insulin antibodies are a cause of hypoglycemia following pancreas transplantation.

OBJECTIVE: Hypoglycemic symptoms have been reported by more than half of pancreas transplantation (PTX) recipients. To better understand the mechanism for the hypoglycemia documented in some of these patients, we studied the glucose and pancreatic hormone response to Sustacal in patients with and without hypoglycemia following PTX. RESEARCH DESIGN AND METHODS: Twelve patients with established, repeated episodes of hypoglycemia following PTX (hypo) were case-matched to PTX recipients without hypoglycemic symptoms (control; n = 7). On the day of the study, fasting glucose, free and total immunoreactive insulin (IRI), C-peptide, proinsulin, and glucagon were drawn (time 0); Sustacal was administered; and glucose, free and total IRI, and C-peptide were assayed at 15, 30, 45, 75, 120, 150, 180, and 240 min. Based on the glucose response to Sustacal, the hypo group was further divided into those whose glucose rose after Sustacal (hypo-high; n = 7) and those with no increase in glucose from baseline concentration (hypo-flat; n = 5). RESULTS: Before the administration of Sustacal, the hypo-high group had a lower fasting free/total IRI (0.26 +/- 0.06, mean +/- SE) than the hypo-flat (0.51 +/- 0.02) or control (0.52 +/- 0.04) groups (both P < 0.05 compared with hypo-high). The glucose response to Sustacal was greatest in the hypo-high group as defined. Area under the curve (AUC) for total IRI following Sustacal was also greatest in the hypo-high group (P < 0.05 compared with both control and hypo-flat groups), but there was no significant difference in free IRI AUC following Sustacal between the three groups. Two individuals developed hypoglycemia during the Sustacal challenge, both in the hypo-high group. CONCLUSIONS: The lower fasting free/total IRI ratio and greater increase in glucose and total IRI in response to Sustacal in the hypo-high group compared with either the hypo-flat or control groups are consistent with the presence of significant quantities of anti-insulin antibodies in the hypo-high group. Because anti-insulin antibodies are, in turn, an established cause of episodic hypoglycemia, this study provides the first data to support the hypothesis that significant quantities of anti-insulin antibodies are a cause of symptomatic hypoglycemia following PTX in some recipients.

Adult↗

Pancreas transplantation: the Nebraska experience.

In summary, we believe that combined PKT can be performed safely and effectively in the absence of uremia, thereby providing the potential for arresting the progression of diabetic complications prior to the development of ESRD. Furthermore, performing solitary PTx prior to the need for a kidney transplant can be accomplished with morbidity and results comparable to PKT. Rehabilitation potential tends to favor patients undergoing either solitary PTx or preemptive PKT. In selected IDDM patients without end-stage diabetic nephropathy, we believe that solitary PTx or PKT are effective treatment options and need not be considered as preemptive, especially in view of increasing waiting times and the variable progressive nature of diabetic complications. As results continue to improve, solitary PTx may offer a potential solution to the growing number of IDDM patients awaiting kidney transplantation in the United States. Ultimately, the role of solitary PTx in the treatment of IDDM will be determined by long-term studies documenting the prevention or arrest of secondary diabetic complications. In the short-term, improvement in quality of life and rehabilitation potential makes preemptive PKT or solitary PTx important therapeutic alternatives for consideration.

Actuarial Analysis↗

Characterization of Vibrio anguillarum strains isolated from diseased fish in Finland.

Characterization of V. anguillarum strains (n = 109) isolated from diseased salmonids was performed. Eight O serovars were found among the strains. Serovar O1 was predominant (90%), while serovars O2, O3, O5, O8, O9, and a new serovar Va NT2, were represented by 1 or 2 strains. Two strains remained non-typeable. One of these was cross-reactive with several antisera, but had a LPS profile identical to that of serovar O8. All serovars showed specific LPS profiles. All but 1 of the O1 strains had a plasmid comparable in size to the pJM1 virulence plasmid, while plasmids of different sizes were found in O2, Va NT2 and the non-typeable strains. Apart from a single strain resistant to tetracycline, all the strains were sensitive to oxolinic acid, tetracycline, and trimethoprim-sulfonamides. By their biochemical and antigenic properties strains causing vibriosis among salmonids in Finland closely resemble Scandinavian strains. Predominance of the serovars O1 and O2 suggests that commercial vaccines containing these serovars should afford sufficient protection against vibriosis in Finland.

Animals↗

Orthotopic hepatic transplantation in patients with type I diabetes mellitus.

Six transplantations of the liver were performed over a period of six years in five adult patients with Type I diabetes mellitus (DM). The diabetic group included two males and three females with a mean age of 36 years and a mean duration of DM of 20 years. Primary diseases of the liver included two instances of primary biliary cirrhosis, two instances of sclerosing cholangitis and one instance of autoimmune chronic hepatitis. Three patients also received a simultaneous whole organ pancreatic transplant. All patients were managed with cyclosporine and prednisone immunosuppression with selective OKT3 induction. Patient and hepatic allograft survival rates were 80 and 67 percent, respectively, after a mean follow-up period of 4.7 years. One of the three pancreatic grafts was successful and resulted in euglycemia for two years. Three patients have subsequently undergone successful renal transplantation at one, two and one-half, and six and one-half years after hepatic transplantation. Although transplantation of the liver can be performed safely in carefully selected patients with Type I DM, these patients are still at risk for the development of progressive nephropathy. Renal transplantation is an acceptable therapeutic alternative when this occurs.

Adult↗

Purification and characterization of IgM-like immunoglobulin from turbot (Scophthalmus maximus L.).

A total of 40 turbot (Scophthalmus maximus) were immunized 3 times during a 3 months period using DNP-HSA whereafter serum samples were collected and pooled. Specific immunoglobulins (Ig) were affinity purified on an agarose column with immobilized DNP-BSA and further purified by gel filtration whereafter monospecific rabbit anti Ig serum was generated. Size exclusion chromatography and non-reduced SDS-PAGE indicated a MW of 8-900 kDa of the dominant antigen binding proteins from turbot serum. Reduced SDS-PAGE showed this fraction to be composed of disulphide linked heavy and light chains with MWs of 79 and 27-29 kDa, respectively, indicating a tetrameric structure. Isoelectric focusing of the 800-900 kDa Ig showed several bands between pH 5.5 and pH 5.8. Mean Ig concentration in serum of 10 turbot was measured to 6.48 mg/ml (SD 5.4) using rocket immunoelectrophoresis. Low molecular weight antigen binding molecules were copurified with the dominating immunoglobulins with an estimated MW of 500 kDa. Reducing SDS-PAGE of this fraction revealed molecules with MWs of 97, 79, 57, 29, and 27 kDa.

Animals↗

Consequences of pancreas transplantation.

PKT has become an important option in selected IDDM patients being considered for kidney transplantation because of its ability to offer superior glycemic control and improved quality of life. As both kidney graft survival and overall mortality are comparable following PKT and kidney transplantation alone at many centers, neither the survival of the patient nor the success of the kidney transplant need be jeopardized by the addition of a pancreas graft. The greater morbidity of PKT can be justified by the evidence that a pancreas graft will prevent recurrent diabetic nephropathy, result in greater improvements in sensory/motor neuropathy, and in some but not all studies, cause greater stabilization of eye disease. Improvements in lipid profiles observed after PKT but not after kidney transplant alone may predict better cardiovascular outcomes as well. Determination of who should receive an isolated pancreas transplant is more complex. Success rates are lower than after PKT. It remains important to ascertain that the candidate is susceptible to diabetic complications, or has repeated bouts of hypoglycemia or ketoacidosis unresponsive to other measures to justify the risks of long-term immuno-suppression. More difficult to determine is whether or when individuals who have advancing diabetic complications yet relatively preserved renal function (creatinine clearance > 70 mL/min) should become candidates. For now, each individual is considered on a case by case basis and the relative risks and benefits for each individual are carefully assessed. However, patient selection will be greatly aided by further research assessing the long-term risks and benefits of all types of pancreas transplantation. Pancreas transplantation will remain an important option in the treatment of IDDM until alternative strategies are developed that can provide equal glycemic control with less or no immunosuppression or less overall morbidity. Most of the research to date has concentrated on the consequences of pancreas transplantation on microvascular complications. However, cardiovascular disease events represent the greatest cause of mortality in pancreas transplant candidates. Thus, changes in cardiovascular risk after pancreas transplantation may be more important to long-term survival than any other factor and should receive greater attention in future studies.

Adolescent↗

Cerebrospinal fluid proteins as indicators of nerve root compression in patients with sciatica caused by disc herniation.

Patients with sciatica caused by lumbar disc herniation were studied to identify biochemical changes in the cerebrospinal fluid related to myelographic findings and clinical observations. One hundred forty-three patients were evaluated by myelography with regard to involvement of the dural sac and the nerve root. A medial group (20 patients) with evidence of dural sac impingement was compared to a lateral group (63 patients) and an extreme lateral group (9 patients) whose condition primarily affected the nerve root. The remaining 51 patients comprised a mixed group with involvement of both the dural sac and the nerve root. The mean cerebrospinal fluid/serum albumin ratio, cerebrospinal fluid/serum immunoglobulin G ratio, and cerebrospinal fluid total proteins showed a significantly increasing trend from the medial through the lateral to the extreme lateral groups. Patients with lateral lumbar disc herniations more often showed neurologic deficits. These results indicate that the elevated cerebrospinal fluid total protein found in the patients with sciatica is due to leaking of plasma proteins primarily from the nerve root into the cerebrospinal fluid. The cerebrospinal fluid proteins may be used as diagnostic parameters of nerve root compression, especially when surgery is a consideration or in patients in whom sciatica is unlikely.

Adolescent↗

Ribotypes and plasmid contents of Vibrio anguillarum strains in relation to serovar.

Eighty-six strains of the 10 major agglutination types of Vibrio anguillarum (serovars O1 to O10) and 6 nontypeable strains of V. anguillarum have been characterized by ribotyping with a probe complementary to 16S and 23S rRNA of Escherichia coli and by plasmid profile analysis. Forty-four different ribotypes were observed with the restriction enzyme HindIII. Ribotype similarity was compared by using the Dice coefficient (Sd), and three significantly different levels of homogeneity within the V. anguillarum serovars were observed (serovars O1, O3A, O7, and O9, Sds of > 90%; serovars O2B, O4, and O10, Sds of 80 to 90%; serovars O2A, O3B, O5, and O8, Sds between 46 and 70%). None of the ribotype patterns of V. anguillarum strains were observed among 20 other Vibrio strains typed for comparison. By cluster analysis, the V. anguillarum strains were divided into a main cluster containing 83 strains, while all strains of serovar O3B, one strain (each) of serovars O2A, O5, and O8, and a nontypeable strain were separated from this cluster by at least 15% difference in similarity coefficients. Plasmids were demonstrated in only six strains other than serovar O1. In serovar O1, a 67- to 70-kilobase-pair (kb) plasmid molecule was present in 17 of 19 strains tested; of the two remaining strains, one strain harbored two plasmids (45 and 6.5 kb) and one strain had no plasmids.

Agglutination Tests↗

Diseases and injuries associated with mortality of hatchery reared Baltic cod (Gadus morhua L.) larvae.

A cod hatching plant was established in 1992 on the island of Bornholm in the Baltic Sea in order to elucidate the possibilities for restocking of cod fry in this brackishwater system. The disease prevalence in 3 batches of hatchery-reared yolksac larvae from the Baltic cod (Gadus morhua L.) was monitored during the posthatch period. High prevalences of bacteriosis/mycosis, lordosis/scoliosis, injuries and protozoan endoparasitism were recorded. Vibrio sp. and Vibrio anguillarum serovar 04, 06, 08 in addition to nontypable strains and saprolegniaceous fungi were isolated from the larvae. The dinoflagellate-like endoparasites were located in the yolksac of the cod larvae.

Animals↗

Results of liver transplantation in diabetic recipients.

BACKGROUND: The results of orthotopic liver transplantation (OLTx) in patients with diabetes mellitus (DM) are not well defined. METHODS: Between 1985 and 1991, 45 adult patients with pretransplantation DM (5 type I, 40 type II) underwent OLTx at our center as identified by retrospective chart review. We compared this diabetic recipient group to a case-control nondiabetic group matched for age, gender, primary liver disease, weight, and timing of OLTx. A total of 30 variables were collected and analyzed with McNemar's test for categorical data, paired t tests for continuous data, and survival and repeated measures analysis for longitudinal data. RESULTS: No differences between diabetic and nondiabetic recipients were noted in patient or graft survival, the incidence or severity of rejection, blood transfusions, operative complications, readmissions, major infections, or number of hospital days after OLTx. However, the incidence of minor bacterial (p = 0.046) and minor fungal (p = 0.035) infections were higher in the DM group. Serum blood urea nitrogen (p = 0.02) and creatinine (p = 0.03) levels were also higher in patients with diabetes versus control patients during the first year after OLTx. CONCLUSIONS: In carefully selected patients with pretransplantation DM, OLTx can be accomplished with results similar to nondiabetic recipients in spite of a higher incidence of minor infections and renal dysfunction.

Diabetes Complications↗