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Biomedical subjects

J Lindberg

Publications and source records attributed to J Lindberg.

At least 19 recordsLinked to original sources
PubMed2006

Surgery for neoplastic changes in ulcerative colitis--can limited resection be justified? Outcome for patients who underwent limited surgery.

BACKGROUND: Patients with ulcerative colitis (UC) are at an increased risk of developing colorectal cancer (CRC). The aim of this study was to investigate the outcome for the patients who underwent limited resection of the colon and/or rectum instead of panproctocolectomy (PPC), with special attention to those with neoplastic changes. METHODS: Since 1977, all known patients with UC from our catchment area have been included in our surveillance programme. A total of 210 patients with UC have been followed up with regular colonoscopies and biopsies. Indications for surgery were severe therapy-resistant disease (TRD), high-grade dysplasia (HGD), CRC or repeated findings of low-grade dysplasia (LGD). Patient compliance was excellent. RESULTS: Fifty-one patients were operated on. In 29 of these patients, PPC was performed initially. At the end-point of the study, additionally seven patients had been radically operated on and three more patients planned to undergo such an operation. Accordingly, 22 patients had their first operation performed as a resection of either a part of or the whole colon or rectum. In this group, there were four patients diagnosed with CRC and three with dysplasia-associated lesion or mass (DALM). One of them died 6 months after surgery because of disseminated CRC, whereas the other patients were alive at the end-point of the study. One of these seven patients with CRC or DALM had at end-point been radically operated on and two patients were awaiting such a procedure (in two patients because of LGD and in one patient because of TRD). Six of the patients who had a colorectal resection performed on the indication of TRD were radically operated later on, five of them because of relapsed TRD and one patient because of LGD in the remaining rectal mucosa. Twenty-one patients gained a mean of 9.4 years with presumably better bowel function, from undergoing a limited resection instead of PPC. None of the patients who underwent a colonic and/or rectal resection died because of CRC or metachronous cancer in their remaining colon or rectum. CONCLUSION: The results of this study indicate that a limited resection of the colon and/or rectum in patients with UC, which requires surgical intervention increases the time with presumably better bowel function and may therefore be an alternative to PPC without increased risk of dying from CRC. This is dependent on the flexibility of the medical service and patient compliance.

Adolescent↗
PubMed2006

Rotational frequency shifts in partially coherent optical fields.

We study the frequency shifts taking place when a random, stationary optical field rotates with respect to an observer. The field is expanded in terms of fully coherent Laguerre-Gaussian basis modes, for which the rotational frequency shifts have been studied previously. We demonstrate the formalism by considering the spectrum of a Gaussian Schell-model field, and show that for a spatially highly incoherent field, significant spectral changes can be expected.

Journal Article↗
PubMed2001

Characterization of galactosyl glycerolipids in the HT29 human colon carcinoma cell line.

Glycoglycerolipids constitute a family of glycolipids with apparently very restricted expression in human tissues. They have previously been detected only in the testis and the nervous system. In the present study, two glycoglycerolipids were isolated from the HT29 human colon carcinoma cell line. The glycoglycerolipids were structurally characterized as a monogalactosylglycerolipid (1-O-alkyl-2-O-acyl-3-O-(beta-galactosyl)-sn-glycerol) and a digalactosylglycerolipid (1-O-alkyl-2-O-acyl-3-O-(beta-galactosyl(1-4)alpha-galactosyl)-sn-glycerol) using NMR and mass spectrometry. This digalactosylglycerolipid has not previously been structurally characterized. When HT29 cells were allowed to differentiate into more enterocyte-like cells by culture in glucose-free medium, expression of both of these glycoglycerolipids was greatly diminished. The presence of glycoglycerolipids in a human colon carcinoma cell line indicates that expression of this family of glycolipids may not be as restricted as previously thought. Instead this class of glycolipids may serve as differentiation antigens in various normal tissues and in tumor development. The Galalpha1-4Gal epitope was previously identified as a receptor for bacterial adhesins and toxins. The finding that this epitope is also linked to a glycerolipid moiety opens up new possible roles for this carbohydrate receptor in intracellular signaling.

Carbohydrate Metabolism↗
PubMed2001

Synthesis of novel, potent, diol-based HIV-1 protease inhibitors via intermolecular pinacol homocoupling of (2S)-2-benzyloxymethyl-4-phenylbutanal.

The synthesis of novel, potent, diol-based HIV-1 protease inhibitors, having phenethyl groups (-CH(2)CH(2)Ph) in P1/P1' position is described. An intermolecular pinacol homocoupling of (2S)-2-benzyloxymethyl-4-phenylbutanal 16 was the key step in the synthesis. From this reaction sequence four carba analogues, compounds 8a, 8b, 9a, and 9b, were prepared, having the inverted configuration of one or both of the stereogenic centers carrying the diol hydroxyls as compared to the parent series represented by inhibitors 6 and 7. Inhibitor 8b was found to be a potent inhibitor of HIV-1 protease (PR), showing excellent antiviral activity in the cell-based assay and in the presence of 40% human serum. The absolute stereochemistry of the central diol of the potent inhibitor (8b) was determined from the X-ray crystallographic structure of its complex with HIV-1 PR.

Amides↗
PubMed2001

Design and synthesis of potent C(2)-symmetric diol-based HIV-1 protease inhibitors: effects of fluoro substitution.

Implementation of derivatized carbohydrates as C(2)-symmetric HIV-1 protease inhibitors has previously been reported. With the objective of improving the anti-HIV activity of such compounds, we synthesized a series of fluoro substituted P1/P1' analogues. These compounds were evaluated for antiviral activity toward both wild type and mutant virus. The potency of the analogues in blocking HIV-1 protease was moderate, with K(i) values ranging from 1 to 7 nM. Nonetheless, compared to the parent nonfluorous inhibitors, a majority of the compounds exhibited improved antiviral activity, for example the 3-fluorobenzyl derivative 9b, which had a K(i) value of 7.13 nM and displayed one of the most powerful antiviral activities in the cellular assay of the series. Our results strongly suggest that fluoro substitution can substantially improve antiviral activity. The X-ray crystal structures of two of the fluoro substituted inhibitors (9a and 9f) cocrystallized with HIV-1 protease are discussed.

Amides↗
PubMed2001

Synthesis and comparative molecular field analysis (CoMFA) of symmetric and nonsymmetric cyclic sulfamide HIV-1 protease inhibitors.

We have previously reported on the unexpected flipped conformation in the cyclic sulfamide class of inhibitors. An attempt to induce a symmetric binding conformation by introducing P2/P2' substituents foreseen to bind preferentially in the S2/S2' subsite was unsuccessful. On the basis of the flipped conformation we anticipated that nonsymmetric sulfamide inhibitors, with P2/P2' side chains modified individually for the S1' and S2 subsites, should be more potent than the corresponding symmetric analogues. To test this hypothesis, a set of 18 cyclic sulfamide inhibitors (11 nonsymmetric and 7 symmetric) with different P2/P2' substituents was prepared and evaluated in an enzyme assay. To rationalize the structure-activity relationship (SAR) and enable the alignment of the nonsymmetric inhibitors, i.e., which of the P2/P2' substituents of the nonsymmetric inhibitors interact with which subsite, a CoMFA study was performed. The CoMFA model, constructed from the 18 inhibitors in this study along with seven inhibitors from previous work by our group, has successfully been used to rationalize the SAR of the cyclic sulfamide inhibitors. Furthermore, from the information presented herein, the SAR of the cyclic sulfamide class of inhibitors seems to differ from the SAR of the related cyclic urea inhibitors reported by DuPont and DuPont-Merck.

Crystallography, X-Ray↗
PubMed2001

A long-term, multicenter study of the efficacy and safety of paricalcitol in end-stage renal disease.

BACKGROUND: Paricalcitol is a vitamin D analog approved for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure. This study was designed to evaluate the long-term efficacy and safety of paricalcitol. Additional analysis evaluated the effects of paricalcitol in hypocalcemic and hyperphosphatemic subpopulations. PATIENTS AND METHODS: One hundred sixty-four end-stage renal disease (ESRD) patiesnts on hemodialysis were treated in an open-label, multicenter study lasting up to 13 months in duration. After a baseline or washout period, an initial starting dose of 0.04-0.393 microg/kg was given 2-3 times per week. This dose was adjusted at the discretion of the investigator according to the patient's intact parathyroid hormone level (iPTH), calcium level, and calcium-phosphorus (Ca x P) product. The therapy was intended to reproduce expected clinical use of paricalcitol. Patients represented a wide cross-section of the ESRD population, and were not excluded from the study based on age or underlying disease. RESULTS: The mean paricalcitol dose level throughout the study was 0.10 microg/kg. The mean iPTH levels (baseline mean 628.3 +/- 27.65 pg/ml) decreased rapidly during the first 4 months of therapy, and reached the designated target range (100-300 pg/ml) by month 5 (mean 295.3 +/- 25.69 pg/ml). A maximum mean decrease in iPTH level of 409 +/- 35.01 pg/ml was seen at month 13. Throughout the course of the study, the mean normalized calcium level was maintained well within the normal range (9.44-9.94 mg/dl). The mean phosphorus level was maintained in an acceptable range throughout the study (5.92-6.53 mg/dl). Mean Ca x P product was maintained between 52 and 65. Mean alkaline phosphatase levels decreased significantly from baseline with a maximum mean decrease of 62 +/- 17.3 U/l observed at month 9. In 34 initially hypocalcemic patients (mean of 7.7 mg/dl) iPTH levels decreased from baseline, on average, by 443 +/- 81.86 pg/ml while mean calcium levels rose by 1.2 +/- 0.23 mg/dl to reach the normal range. In 35 initially hyperphosphatemic patients (mean of 8.0 mg/dl) iPTH levels decreased, on average, by 515 +/- 103.31 pg/ml with an associated mean decrease in phosphorus of 0.57 +/- 0.52 mg/dl. Adverse events that were considered by the investigator to have a possible. probable, or definite relationship to study drug occurred in 26% of patients. Other than expected temporary effects of hypercalcemia and hyperphosphatemia. the only possible trends for causally-related adverse events were for nausea/vomiting and metallic taste. CONCLUSIONS: This long-term study of paricalcitol demonstrates that it rapidly and effectively suppresses iPTH levels in a wide spectrum of ESRD patients and caused no unexpected adverse events.

Adult↗
PubMed2001

Treatment strategies for renal bone disease.

Renal bone disease encompasses a wide range of bone abnormalities that are intricately linked with metabolic systems that are driven by calcium, phosphorus, PTH, and D hormone levels. An integrated approach to treatment must involve both dietary measures, use of phosphate binders as appropriate, and D hormone replacement. Not incidentally, implementation of this integrated approach involves not only our patients but everyone associated in their care, especially the nephrologist, nephrology nurse, and renal dietitians. Improving patient outcomes--preventing or minimizing renal bone disease and the complications of secondary hyperparathyroidism--will require communication and cooperation between all of us on behalf of our patients.

Chronic Kidney Disease-Mineral and Bone Disorder↗
PubMed2000

[Increased procalcitonin level in bacteriogenic metabolic disturbances. A new possibility for diagnosis and treatment monitoring in sepsis].

Earlier observations of increased plasma concentrations of immunoreactive calcitonin (32 amino acids) in sepsis and other non-tumorous conditions may be explained by increased secretion of procalcitonin, the 116-amino acid prohormone. At present, the site(s) of origin of procalcitonin in sepsis, the factors regulating its biosynthesis and release, the route(s) of its elimination from blood as well as its biological function(s) are unknown. The rapid increase in procalcitonin concentration in sepsis--in some patients earlier than that of C-reactive protein--and decrease upon successful chemotherapy makes procalcitonin a potentially important biomarker in monitoring patients with suspected or confirmed sepsis.

Biomarkers↗
PubMed2000

Research directions: new clinical frontiers.

One of the greatest remaining challenges facing nephrology research is obtaining data with detail and precision for the three large, yet "forgotten," populations that span the spectrum of kidney disease: patients with chronic renal insufficiency (CRI), peritoneal dialysis patients, and kidney transplant patients. Studies of these populations, particularly the CRI group, are hampered by the relative mobility of these patients, the lack of stringent epidemiologic or clinical definitions, and the tendency to extrapolate data from hemodialysis populations into other clinical settings. This article suggests a two-pronged approach to a research agenda: first, by recognizing the need for better data regarding the natural history of these kidney failure subsets and their comorbidities; and second, by directing greater effort at identifying rational, efficacious, and cost-effective interventions to influence their natural history positively. Specific efforts are suggested in all three populations. For patients with CRI, studies should be directed at (1) identifying high-risk patients; (2) determining methods for making optimal referrals to the nephrologist; (3) identifying and managing CRI, its complications, and its comorbid conditions; and (4) establishing processes for the smooth transition to dialysis. The peritoneal dialysis population will benefit from studies addressing the treatment of anemia and its ability to modify cardiovascular illness and quality of life. Kidney transplant studies should also focus on the identification and management of comorbid conditions, as well as the effects of various interventions on quality of life. Rational evidence-based care of these conditions, which are critically important to patients, their families, and the health care system in general, must await the conduct of well-designed prospective observational and interventional trials.

Humans↗
PubMed1999

[Hepatitis G virus exists--but does hepatitis G?].

Hepatitis G virus, or GB virus type C, is a recently discovered RNA virus, remotely related to hepatitis C virus. The infection is frequently found, and seems to be blood-borne, occurring among intravenous drug abusers and transmitted from mother to child. Although long-term viraemia is common, in most cases the infection resolves spontaneously. Whether the viral infection causes liver disease or has other manifestations remains unknown.

Adult↗
PubMed1999

Racial differences in bone mineral density and bone loss among end-stage renal disease patients.

Although black patients without end-stage renal disease (ESRD) have a greater bone mineral density (BMD) than whites, the impact of race on BMD among patients with ESRD who are likely to have varying degrees of renal osteodystrophy is not known. We undertook a cohort study of 106 hemodialysis patients comparing BMD and bone loss between black and white patients with ESRD to determine if black patients have a greater BMD and less bone loss than white patients with ESRD. BMD was determined by dual-energy radiograph absorptiometry (DEXA). Osteopenia was defined as greater than 1 standard deviation (SD) less than the mean of peak bone mass (T score <-1), and osteoporosis was defined as greater than 2.5 SDs less than the mean of peak bone mass (T score <-2.5). The association between BMD and race was estimated using linear regression. The risk for osteopenia among black compared with white patients was calculated using logistic regression. Black patients were similar to white patients with respect to all characteristics noted, except black patients were less likely to be men (69.7% v 49. 4%) and tended to have greater intact parathyroid hormone (PTH) values (mean, 403.2 +/- 384.5 pg/mL v 161.4 +/- 129.0 pg/mL). Compared with whites, the BMD of blacks was a mean of 1.15 (95% confidence interval [CI], 0.54 to 1.78) SDs greater at the femoral neck after adjusting for age, PTH level, and sex. The percentage of bone loss per year was similar between blacks and whites. The risk for osteopenia among blacks was significantly less than that among whites (odds ratio = 0.15; 95% CI, 0.04 to 0.59) after adjusting for age, sex, and PTH level. Black patients with ESRD have a greater BMD and are at decreased risk for osteopenia compared with whites, independent of renal osteodystrophy. When considering bone disease among patients with ESRD, physicians should also consider osteoporosis and the impact of race on BMD.

Bone Density↗
PubMed1999

Recurrent endocarditis caused by Streptococcus pneumoniae.

Pneumococcal endocarditis most often presents as an ulcerative endocarditis causing rapid destruction of the normal aortic valve, leading to aortic insufficiency and acute heart failure. Alcoholism is the most frequent underlying medical condition. This case illustrates that pneumococcal endocarditis can reoccur and is able to attack healthy, as well as previously damaged, heart valves. It also illustrates that vaccination of certain groups should be considered. The importance of repeated heart stethoscopy in patients with pneumococcaemia is emphasized.

Anti-Bacterial Agents↗
PubMed1999

Chronic hepatitis B in children in Gothenburg, Sweden.

Sweden is a low prevalence area for hepatitis B, but the number of chronic carriers has increased during the last decade due to immigration. Out of a total of 120 children with identified chronic hepatitis B in Gothenburg, Sweden, 93 were investigated during the 2-year period 1994-95. The children had a mean age of 10.9 years and originated from 21 different countries. Most infections were discovered during various screening programmes after arrival in Sweden. A total of 90 of the 93 children were HBV-DNA positive by Amplicor HBV Monitor (Roche Diagnostics) and 58% (54/93) were HBeAg positive. All children either originated from areas with a high or medium prevalence of HBV infection (81/93, 87%) or were born in Sweden to mothers originating from high or medium prevalence countries (12/93, 13%). Three of these 12 children were vertically infected in spite of adequate immunoprophylaxis and 8 were born to mothers with undiscovered chronic HBV infection. In all, 34 children had mothers who were HBsAg positive. No overt case of transmission was notified in day-care centres or schools, or from a child to a non-immune parent. None of the children reported any symptoms of liver disease, but 38% (35/93) had elevated aminotransferases. Therefore, screening programmes are essential to identify chronic HBV infection in children in order to prevent transmission and to find individuals at risk of progressive liver damage who should be considered for treatment.

Acute Disease↗
PubMed1999

Natural killing of MHC class I(-) lymphoblasts by NK cells from long-term bone marrow culture requires effector cell expression of Ly49 receptors.

NK cells from long-term bone marrow culture (LTBMC) were compared with IL-2-activated splenic NK cells [short-term spleen cell culture (STSC)] with regard to expression of inhibitory Ly49 receptors and cytotoxic function. In the LTBMC, the total number of NK cells expressing either one of the Ly49 molecules A, C/I and G2 was strongly reduced (10-15% of NK1.1(+) cells) compared to the STSC (80-90% of NK1.1(+) cells). With regard to cytotoxic function, we confirmed that LTBMC-derived NK cells efficiently killed the prototype NK target YAC-1. However, against other targets, killing was more variable. First, while STSC-derived NK cells clearly distinguished MHC class I(-) from MHC class I(+) tumor cell targets, LTBMC-derived NK cells did not; they either killed both targets equally well or not at all. Secondly, LTBMC-derived NK cells were largely incapable of killing lymphoblast targets deficient in MHC class I expression. To test whether this cytotoxic defect was due to the low number of Ly49(+) NK cells in the LTBMC, we separated Ly49(+) and Ly49(-) NK cells by cell sorting and tested them individually. This experiment showed that only Ly49(+) NK cells in the LTBMC were able to kill MHC class I(-) lymphoblasts (and to distinguish them from MHC class I(+)), despite good cytotoxicity against YAC-1 cells in both populations. These data suggest that certain modes of NK cell triggering are dependent on Ly49 receptor expression. From our results, we speculate that inhibitory receptors are expressed before triggering receptors for normal self cells during NK cell development, which may be an important mechanism to preserve self tolerance during the early stages of NK cell maturation.

Animals↗
PubMed1999

Advances in photoacoustic noninvasive glucose testing.

We report here on in vitro and in vivo experiments that are intended to explore the feasibility of photoacoustic spectroscopy as a tool for the noninvasive measurement of blood glucose. The in vivo results from oral glucose tests on eight subjects showed good correlation with clinical measurements but indicated that physiological factors and person-to-person variability are important. In vitro measurements showed that the sensitivity of the glucose measurement is unaffected by the presence of common blood analytes but that there can be substantial shifts in baseline values. The results indicate the need for spectroscopic data to develop algorithms for the detection of glucose in the presence of other analytes.

Acoustics↗