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Biomedical subjects

K Link

Publications and source records attributed to K Link.

At least 19 recordsLinked to original sources
PubMed2006

Risk for severe hypoglycaemia with unawareness in GH-deficient patients during the insulin tolerance test.

OBJECTIVE: The insulin tolerance test (ITT) has been suggested as the gold standard for diagnosing GH deficiency (GHD). The ITT is, however, potentially hazardous. Glucose monitoring during the ITT varies between centres and there is surprisingly little information on the actual level of blood glucose nadir and the duration of hypoglycaemia in patients undergoing the ITT. The aim of the present study was to closely monitor the blood glucose level and to register the presence of symptoms and signs of hypoglycaemia during the ITT. DESIGN AND PATIENTS: Sixteen patients (seven women), aged 22-59 years were consecutively recruited for an ITT, and showed GHD (peak GH < 3 microg/l). RESULTS: In five (31%) of the patients unawareness of hypoglycaemia was recorded, the median nadir blood glucose level was 1.4 mmol/l (range 1.1-1.9) and the duration of blood glucose < 2.2 mmol/l was 25 min (range 20-33). The remaining 11 patients were symptomatic, and tiredness (n=6) and dizziness (n=3) were the most frequent symptoms. In these symptomatic patients the median nadir blood glucose level was 1.3 mmol/l (range 1.0-1.6) and the duration of blood glucose < 2.2 mmol/l was 25 min (range 15-30). CONCLUSIONS: In patients with GHD subjected to the ITT, symptoms of hypoglycaemia were scarce and a third showed unawareness. Close blood glucose monitoring is recommended at the ITT as low nadir blood glucose levels and long duration of hypoglycaemia may be present irrespective of symptoms of hypoglycaemia. Recommendations for intervention with intravenous glucose, at unacceptable low blood glucose levels or at prolonged hypoglycaemia, are warranted.

Adult↗
PubMed2001

Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial.

BACKGROUND: The role of adjuvant treatment in pancreatic cancer remains uncertain. The European Study Group for Pancreatic Cancer (ESPAC) assessed the roles of chemoradiotherapy and chemotherapy in a randomised study. METHODS: After resection, patients were randomly assigned to adjuvant chemoradiotherapy (20 Gy in ten daily fractions over 2 weeks with 500 mg/m(2) fluorouracil intravenously on days 1-3, repeated after 2 weeks) or chemotherapy (intravenous fluorouracil 425 mg/m(2) and folinic acid 20 mg/m(2) daily for 5 days, monthly for 6 months). Clinicians could randomise patients into a two-by-two factorial design (observation, chemoradiotherapy alone, chemotherapy alone, or both) or into one of the main treatment comparisons (chemoradiotherapy versus no chemoradiotherapy or chemotherapy versus no chemotherapy). The primary endpoint was death, and all analyses were by intention to treat. Findings 541 eligible patients with pancreatic ductal adenocarcinoma were randomised: 285 in the two-by-two factorial design (70 chemoradiotherapy, 74 chemotherapy, 72 both, 69 observation); a further 68 patients were randomly assigned chemoradiotherapy or no chemoradiotherapy and 188 chemotherapy or no chemotherapy. Median follow-up of the 227 (42%) patients still alive was 10 months (range 0-62). Overall results showed no benefit for adjuvant chemoradiotherapy (median survival 15.5 months in 175 patients with chemoradiotherapy vs 16.1 months in 178 patients without; hazard ratio 1.18 [95% CI 0.90-1.55], p=0.24). There was evidence of a survival benefit for adjuvant chemotherapy (median survival 19.7 months in 238 patients with chemotherapy vs 14.0 months in 235 patients without; hazard ratio 0.66 [0.52-0.83], p=0.0005). Interpretation This study showed no survival benefit for adjuvant chemoradiotherapy but revealed a potential benefit for adjuvant chemotherapy, justifying further randomised controlled trials of adjuvant chemotherapy in pancreatic cancer.

Adenocarcinoma↗
PubMed2001

Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women.

CONTEXT: Herpes simplex virus type 2 (HSV-2) is one of the most common sexually transmitted infections in the United States. No prospective study has shown the ability of condoms to reduce transmission of HSV-2. OBJECTIVE: To evaluate risk factors for HSV-2 acquisition and efficacy of condoms in prevention of HSV-2 transmission. DESIGN: Analysis of data from a randomized, double-blind, placebo-controlled trial conducted December 13, 1993, to June 28, 1996, of an ineffective candidate HSV-2 vaccine with 18 months of follow-up. SETTING: Eighteen clinical trial centers in the United States. PARTICIPANTS: A total of 528 monogamous couples discordant for HSV-2 infection, including an HSV-2-susceptible population of 261 men and 267 women. MAIN OUTCOME MEASURE: Acquisition of HSV-2 infection by susceptible partners, compared with those remaining free of HSV-2 with regard to demographic characteristics, sexual activity, and condom use. RESULTS: Twenty-six women (9.7%) vs 5 men (1.9%) acquired HSV-2, for a rate per 10 000 sex acts (episodes of sexual intercourse) of 8.9 vs 1.5, respectively (P<.001). In multivariable analysis, younger age (adjusted hazard ratio [HR] per 5 years, 1.57; 95% confidence interval [CI], 1.22-2.04), seropositivity for HSV-1 and HSV-2 vs HSV-2 alone in the source partner (adjusted HR, 2.34; 95% CI, 1.14-4.82), and more frequent sexual activity (adjusted HR per additional sex act per week, 1.10; 95% CI, 1.01-1.19) were associated with higher risk of HSV-2 acquisition. Condom use during more than 25% of sex acts was associated with protection against HSV-2 acquisition for women (adjusted HR, 0.085; 95% CI, 0.01-0.67) but not for men (adjusted HR, 2.02; 95% CI, 0.32-12.50). Risk of HSV-2 transmission declined from 8.5 per 100 person-years in the initial 150-day interval to 0.9 per 100 person-years in the final 150-day interval (P =.002 for trend), concurrent with a decrease in sexual activity and proportion of sex acts occurring when the source partner had genital lesions. CONCLUSIONS: Condom use offers significant protection against HSV-2 infection in susceptible women. Changes in sexual behavior, correlated with counseling about avoiding sex when a partner has lesions, were associated with reduction in HSV-2 acquisition over time. These data suggest that identification of discordant couples can reduce transmission of HSV-2, especially for heterosexual couples in which the male partner has HSV-2 infection.

Acyclovir↗
PubMed2001

Formation of the single-layer beta-sheet of Borrelia burgdorferi OspA in the absence of the C-terminal capping globular domain.

Borrelia outer surface protein A (OspA) contains a unique single-layer beta-sheet that connects N and C-terminal globular domains. This single-layer beta-sheet segment (beta-strands 8-10) is highly stable in solution, although it is exposed to the solvent on both faces of the sheet and thus it does not contain a hydrophobic core. Here, we tested whether interactions with the C-terminal domain are essential for the formation of the single-layer beta-sheet. We characterized the solution structure, dynamics and stability of an OspA fragment corresponding to beta-strands 1-12 (termed OspA[27-163]), which lacks a majority of the C-terminal globular domain. Analyses of NMR chemical shifts and backbone nuclear Overhauser effect (NOE) connectivities showed that OspA[27-163] is folded except the 12th and final beta-strand. (1)H-(15)N heteronuclear NOE measurements and amide H-(2)H exchange revealed that the single-layer beta-sheet in this fragment is more flexible than the corresponding region in full-length OspA. Thermal-denaturation experiments using differential scanning calorimetry and NMR spectroscopy revealed that the N-terminal globular domain in the fragment has a conformational stability similar to that of the same region in the full-length protein, and that the single-layer beta-sheet region also has a modest thermal stability. These results demonstrate that the unique single-layer beta-sheet retains its conformation in the absence of its interactions with the C-terminal domain. This fragment is significantly smaller than the full-length OspA, and thus it is expected to facilitate studies of the folding mechanism of this unusual beta-sheet structure.

Amino Acid Sequence↗
PubMed2001

Low individualized growth hormone (GH) dose increased renal and cardiac growth in young adults with childhood onset GH deficiency.

OBJECTIVE: In childhood onset GH deficiency (GHD) a reduction in left ventricular mass (LV-mass) and impairment of systolic function as well an impairment in glomerular filtration rate (GFR) has been shown. The aim of the present study was to assess if a low GH dose resulted in an improvement in morphological and functional parameters of these organs. DESIGN AND PATIENTS: Eleven patients with childhood onset GHD were investigated before and after 10 months of GH treatment at a dose of 1.5 IU/day (range 1-2), corresponding to 0.02 IU/kg/day or 7 microg/ kg/day. The GH dose resulted in a serum IGF-I level in the normal range in all but one patient. MEASUREMENTS: Doppler echocardiography of the heart and ultrasound examination of the kidneys was performed. Glomerular filtration rate (GFR) was estimated with iohexol clearance and urinary proteinuria was measured with 24-h urinary samples collected for analyses of albumin, alpha-1-microglobulin, IgG and albumin/creatinine clearance ratio. Body composition was measured by bioelectric impedance analysis. RESULTS: L V-mass index increased significantly after GH treatment (P = 0.04), and there was a clear trend for a positive correlation between the increase in serum IGF-I and the increase in LV-mass index, although it did not reach significance (r= 0.57, P = 0.07). GH treatment did not increase cardiac fractional shortening. Kidney length increased significantly (P = 0.02) with an average increase of 1 cm (range - 0.5-1.5 cm). No significant changes in median GFR or serum creatinine were recorded. Three patients with subnormal GFR before GH treatment normalized after 10 months of treatment. Urine analysis showed no abnormalities before or after GH treatment. A significant decrease in percentage fat mass was recorded (P = 0.03). CONCLUSION: A low individualized GH dose to adults with childhood onset GHD resulted in an increase in LV-mass index and kidney length. Re-establishing GH treatment with a low dose in this patient group can lead to a further somatic maturation of these organs, probably not accomplished previously.

Adolescent↗
PubMed2000

Design of single-layer beta-sheets without a hydrophobic core.

The hydrophobic effect is the main thermodynamic driving force in the folding of water-soluble proteins. Exclusion of nonpolar moieties from aqueous solvent results in the formation of a hydrophobic core in a protein, which has been generally considered essential for specifying and stabilizing the folded structures of proteins. Outer surface protein A (OspA) from Borrelia burgdorferi contains a three-stranded beta-sheet segment which connects two globular domains. Although this single-layer beta-sheet segment is exposed to solvent on both faces and thus does not contain a hydrophobic core, the segment has a high conformational stability. Here we report the engineering of OspA variants that contain larger single-layer beta-sheets (comprising five and seven beta-strands) by duplicating a beta-hairpin unit within the beta-sheet. Nuclear magnetic resonance and small-angle X-ray scattering analyses reveal that these extended single-layer beta-sheets are formed as designed, and amide hydrogen-deuterium exchange and chemical denaturation show that they are stable. Thus, interactions within the beta-hairpin unit and those between adjacent units, which do not involve the formation of a hydrophobic core, are sufficient to specify and stabilize the single-layer beta-sheet structure. Our results provide an expanded view of protein folding, misfolding and design.

Antigens, Surface↗
PubMed1999

Bacterial complications of strongyloidiasis: Streptococcus bovis meningitis.

We report the case of a 64-year-old veteran who had Streptococcus bovis meningitis as a result of a long latent Strongyloides infection that became acute when he was treated with prednisone. We reviewed 38 reported cases of serious bacterial infections associated with strongyloidiasis. Patients most frequently had nonspecific gastrointestinal symptoms. Of these 38 patients, 21 (55%) had meningitis, and 28 (73%) had bacteremia that was polymicrobial in 3 cases (8%). Other sites of infection included lung, bone marrow, ascites, mitral valve, and lymph node. Most infections were due to enteric gram-negative bacteria. There is one previously reported case of S bovis meningitis. Thirty-four of the patients (89%) were immunosuppressed; 21 of these (55%) were taking pharmacologic doses of adrenal corticosteroids. Thirty-three of the 38 (87%) patients died. Patients with enteric bacterial infection without an obvious cause should be tested for the presence of strongyloidiasis.

Animals↗
PubMed1997

Progress report. A randomized multicenter European study comparing adjuvant radiotherapy, 6-mo chemotherapy, and combination therapy vs no-adjuvant treatment in resectable pancreatic cancer (ESPAC-1).

CONCLUSION: The ESPAC-1 trial is the largest study of its kind in pancreatic cancer and should definitively address the question of the role of conventional methods of adjuvant treatment in pancreatic cancer. BACKGROUND: At the joint International Association of Pancreatology and the European Pancreatic Club meeting in Mannheim, Germany (June 12-15, 1996) a satellite meeting of the European Study Group for Pancreatic Cancer (ESPAC) met to discuss the progress of the ESPAC-1 trial. METHODS: A randomized multicenter study to address which, if any, of the following adjuvant treatments are of benefit in patients with resectable pancreatic cancer: radiotherapy (40 Gy with 5-FU as a sensitizing agent), 6 mo of chemotherapy (5-FU and folinic acid), or a combination of these treatments. RESULTS: From February 1994 to June 1996 (the time of the Mannheim meeting) 221 patients so far have been recruited into the three treatment arms and one control arm.

Adenocarcinoma↗
PubMed1997

ESPAC-1 trial progress report: the European randomized adjuvant study comparing radiochemotherapy, 6 months chemotherapy and combination therapy versus observation in pancreatic cancer.

At the joint International Association of Pancreatology and European Pancreatic Club meeting at King's College, London (July 9-12, 1997), a satellite meeting of the European Study Group for Pancreatic Cancer (ESPAC) met to discuss the progress of the ESPAC-1 trial. This study will address which, if any, of the following adjuvant treatments are of benefit in patients with resectable pancreatic cancer: radiotherapy (40 Gy with 5-fluorouracil as a sensitising agent); 6 months chemotherapy (5-fluorouracil and folinic acid), or a combination of these treatments. The study, which commenced in 1994, had already recruited 348 patients into the 3 treatment arms and 1 control arm of the study by May 31, 1997. This is the largest study of its kind in pancreatic cancer and should definitively address the question of the role of conventional methods of adjuvant treatment in pancreatic cancer.

Chemotherapy, Adjuvant↗
PubMed1997

Postictal neurogenic pulmonary edema: experience from an ECT model.

Neurogenic pulmonary edema (NPE) is thought to rarely occur after seizures. Paradoxically, NPE is frequently found (>80%) at autopsy in epileptic patients who die unexpectedly. The reason for the discrepancy between the frequency of NPE found at autopsy and that after uncomplicated seizures is unclear. The literature suggests that subclinical NPE occurs rarely after uncomplicated seizures and resolves within a few hours, but is undetected because of infrequent use of routine chest radiographs early after a seizure occurs. This pilot study examined the frequency of subclinical, radiographically confirmed NPE after electroconvulsive therapy (ECT)-induced seizures. If shown to occur, ECT-induced subclinical NPE would provide an easily reproducible model to study NPE after seizures in patients with epilepsy. Given that sudden unexplained death syndrome accounts for approximately 10% of the deaths in patients with epilepsy, an easily reproducible model for NPE would have heuristic value. We examined 12 patients undergoing ECT for depression with chest radiographs before and after ECT. In this group, only 1 of the 12 patients had subclinical NPE in their post-ECT radiograph. We conclude that subclinical NPE does not significantly occur after seizures in patients undergoing ECT and therefore, would not serve as an application for research.

Aged↗
PubMed1995

[Clinical studies of the incidence of pulmonary and extrapulmonary tuberculosis].

On the whole 797 patients (mean age 49.5 +/- 18.6 years) with tuberculosis who were hospitalized during 1987 and the first half of the year 1994 were investigated. 148 (18.6%) of these patients were foreigners. Regarding the age, the patients of German origin were mostly above 40 years (70.5%). Within the group of foreigners, 61.5% were below 40 years. 83.3% of the patients suffered from pulmonary and 11.4% from extrapulmonary and 11.4% from extrapulmonary tuberculosis. 5.3% of these patients had both manifestations. The tuberculin tine test was positive in 95.7% and negative in 4.3%. In 63.9% of all patients the tuberculosis was localized in the upper lobe of the lung. The tuberculosis was established bacteriologically in 56.0% and histologically in 16.5%. Both methods were applied in 13.6%. The tuberculosis was deteriorated by chronic alcoholism. Malignant diseases were recorded in 17 (2.1%) of the patients. 22 (2.8%) died during their stay at the hospital.

Adult↗
PubMed1991

Rapid antimicrobial susceptibility testing of gram-negative bacilli using Baxter MicroScan rapid fluorogenic panels and autoSCAN-W/A.

The MicroScan Rapid Neg MIC/Combo panels and autoSCAN-W/A (Walk Away) system utilize automated fluorescence technology for rapid antimicrobial susceptibility testing of Gram-negative bacilli. In a three site clinical study eleven antimicrobial agents were evaluated by comparing results obtained with 741 clinical isolates, using rapid fluorogenic expanded dilution MIC panels and corresponding frozen microdilution reference panels determined visually. Results for 31%, 40%, 12% and 9% of the isolates were available within 3.5, 4.5, 5.5 and 7.0 hours respectively. Results for 7.3% were not available within that time period. For the seven drugs analyzed using a Minimum Inhibitory Concentration range of dilutions, overall agreement (+/- 1 dilution) was 94%, with 1.5% very major, 0.9% major and 2.5% minor errors. For the four drugs analyzed using a Breakpoint range of dilutions, overall agreement (+/- 1 dilution) was 97%, with two percent very major, and one percent major errors. The MicroScan Rapid Neg MIC system is an accurate and rapid method for same day determination of susceptibility of Gram-negative bacilli.

Anti-Bacterial Agents↗
PubMed1991

Primary care and the asymptomatic HIV patient.

Most patients with HIV infections are asymptomatic or minimally symptomatic. Primary care physicians can play a unique and vital role in their care. They should: 1. Look for cases. Treatment can prevent or delay progression of disease. 2. Know how to interpret the serologic tests for HIV infection. 3. Collect an adequate data base to assess extent and severity of disease and screen for certain coexisting infections. 4. Intervene appropriately with counseling and prophylactic therapy. 5. Refer early when neoplasia, opportunistic infections, or diagnostic uncertainties occur.

HIV Infections↗
PubMed1990

Sleep modulation of neuroendocrine function: developmental changes in gonadotropin-releasing hormone secretion during sexual maturation.

To assess sleep-associated changes in gonadotropin-releasing hormone secretion during sexual maturation, we studied nighttime and daytime patterns of LH and FSH secretion in two groups with qualitatively similar sex steroid levels: girls with central precocious puberty and young adult women in the early follicular phase of an ovulatory menstrual cycle. In the girls with central precocious puberty, all indices of LH secretion were significantly higher at night than during the day (mean LH levels, 12 +/- 2 versus 5 +/- 1 IU/L, p less than or equal to 0.01; LH pulse amplitude 16 +/- 2 versus 7 +/- 1 IU/L, p less than or equal to 0.01; and LH pulse frequency 0.70 +/- 0.05 versus 0.35 +/- 0.08 pulse/patient-h, p less than or equal to 0.01). Girls with a history of menses, who were presumably the most mature, lacked this diurnal variability. Mean nocturnal FSH levels were only slightly higher than daytime levels (7.6 +/- 0.5 versus 7.2 +/- 0.5 IU/L, p less than or equal to 0.05) resulting in alternating periods of LH (nighttime) and FSH (daytime) predominance in this pubertal population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Testosterone and oxandrolone, a nonaromatizable androgen, specifically amplify the mass and rate of growth hormone (GH) secreted per burst without altering GH secretory burst duration or frequency or the GH half-life.

We investigated the mechanisms by which androgens increase mean circulating GH concentrations in boys. We tested two hypotheses: 1) testosterone increases serum GH concentrations at least in part via an androgen receptor-mediated mechanism, rather than exclusively by way of aromatization to estrogen; 2) androgen augments one or more specific features to GH secretion (secretory burst number, amplitude, and/or duration) and/or prolongs the half-life of GH removal. To examine these hypotheses, prepubertal boys with constitutionally delayed development and/or growth were given injections of testosterone (100 mg monthly; n = 7) or treated with oral oxandrolone, a nonaromatizable androgen (1.25 mg twice daily; n = 5). Pulsatile GH release was studied before and during androgen administration by sampling blood at 20-min intervals for 24 h. The immunoreactive GH time series were subjected to a novel deconvolution technique, which revealed that 1) testosterone and oxandrolone each increased mean (24-h) serum GH concentrations significantly; 2) both androgens augmented the daily endogenous GH secretory rate significantly; 3) increased GH production resulted from a higher mass of GH secreted per burst and a higher maximal rate of GH secretion within each burst; and 4) androgens amplified the magnitude of the nyctohemeral rhythm in the mass (but not frequency) of GH secretory pulses. The observed effects of androgen were specific, since the number and duration of GH secretory bursts and the subject-specific GH half-life were unaltered by androgen treatment. We conclude that androgen acting apart from conversion to estrogen is capable of specifically activating the somatotropic axis via distinct neuroendocrine secretory mechanisms.

Adolescent↗