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J B Sørensen

Publications and source records attributed to J B Sørensen.

At least 19 recordsLinked to original sources
PubMed2006

Munc18-1 phosphorylation by protein kinase C potentiates vesicle pool replenishment in bovine chromaffin cells.

Activation of protein kinase C (PKC) after robust stimulation is necessary for vesicle pool replenishment in secretory cells. Here we studied the contribution of a prominent downstream PKC target, Munc18-1, to this process in bovine chromaffin cells. In these cells, both activation of endogenous PKC and overexpressing of Munc18-1 promote vesicle pool replenishment after an extensive stimulation. In order to study the physiological relevance of PKC-dependent Munc18-1 phosphorylation, we generated two Munc18-1 phospho-mutants; one that mimics a constitutively PKC-phosphorylated Munc18-1 (i.e. a phosphomimetic mutant; Munc18-1(S313D)) and a second that cannot be PKC-phosphorylated (Munc18-1(3A)). Overexpression of Munc18-1(3A) caused a significant decrease in vesicle pool replenishment following a depleting stimulation, while Munc18-1(S313D) caused a significant increase in vesicle pool replenishment. These findings suggested that the phosphorylation of Munc18-1 by PKC potentiates vesicle pool replenishment. This hypothesis was further strengthened by the finding that overexpression of wild type Munc18-1 in the presence of a PKC inhibitor caused a significant reduction in vesicle pool replenishment, similar to that observed with Munc18-1(3A). Moreover, overexpression of Munc18-1(S313D) in the presence of the PKC inhibitor partly alleviated this attenuation, elucidating Munc18-1's unique contribution to vesicle pool replenishment. Finally, we demonstrate that Munc18-1 promotes vesicle docking in a phosphorylation-independent manner. This is deduced from the findings that both the wild type and the two Munc18-1 phospho-mutants enhanced docking to the same extent in bovine chromaffin cells. We conclude that Munc18-1 facilitates docking in a PKC phosphorylation-independent manner, and that its phosphorylation by PKC potentiates vesicle pool replenishment following a depleting stimulation, at a post-docking stage.

Adrenal Medulla↗
PubMed2005

Prior heavy exercise eliminates VO2 slow component and reduces efficiency during submaximal exercise in humans.

We investigated the hypothesis that the pulmonary oxygen uptake (VO2) slow component is related to a progressive increase in muscle lactate concentration and that prior heavy exercise (PHE) with pronounced acidosis alters VO2 kinetics and reduces work efficiency. Subjects (n= 9) cycled at 75% of the peak VO2 (VO2peak) for 10 min before (CON) and after (AC) PHE. VO2 was measured continuously (breath-by-breath) and muscle biopsies were obtained prior to and after 3 and 10 min of exercise. Muscle lactate concentration was stable between 3 and 10 min of exercise but was 2- to 3-fold higher during AC (P < 0.05 versus CON). Acetylcarnitine (ACn) concentration was 6-fold higher prior to AC and remained higher during exercise. Phosphocreatine (PCr) concentration was similar prior to exercise but the decrease was 2-fold greater during AC than during CON. The time constant for the initial VO2 kinetics (phase II) was similar but the asymptote was 14% higher during AC. The slow increase in VO2 between 3 and 10 min of exercise during CON (+7.9 +/- 0.2%) was not correlated with muscle or blood lactate levels. PHE eliminated the slow increase in VO2 and reduced gross exercise efficiency during AC. It is concluded that the VO2 slow component cannot be explained by a progressive acidosis because both muscle and blood lactate levels remained stable during CON. We suggest that both the VO2 slow component during CON and the reduced gross efficiency during AC are related to impaired contractility of the working fibres and the necessity to recruit additional motor units. Despite a pronounced stockpiling of ACn during AC, initial VO2 kinetics were not affected by PHE and PCr concentration decreased to a lower plateau. The discrepancy with previous studies, where initial oxidative ATP generation appears to be limited by acetyl group availability, might relate to remaining fatiguing effects of PHE.

Adaptation, Physiological↗
PubMed2004

Patient-physician communication concerning participation in cancer chemotherapy trials.

Cancer patients demand a high level of involvement in decisions concerning treatment. Many patients are informed about experimental trials, and especially the first consultation may be crucial for the future communication and treatment process. Patients with nonresectable non-small-cell lung cancer or colorectal cancer informed about experimental chemotherapy completed a questionnaire on satisfaction with the communication process, general attitude towards experimental treatments, the substance of information, and personal contact with the physician following their first consultation in a medical oncology unit. Physicians completed a questionnaire on their perception of the patients' satisfaction. Among 68 physician-cancer patient pairs, 29 patients were informed on chemotherapy in randomised trials and 39 in nonrandomised studies. The general attitude towards experimental treatment was positive or very positive in 71% of patients. Information on the treatment was perceived as completely adequate in 93% of patients informed on randomised and in 67% informed on nonrandomised trials. Physicians underestimated the patients' satisfaction with the overall communication process, the personal contact, the patients' perceived sufficiency of the specific treatment information and their ability to decide on study entry. In conclusion, considerable differences were observed between patients informed about experimental chemotherapy in randomised and nonrandomised trials, both with respect to their perception of how adequate the information on the specific treatments were, and whether it was sufficient for decisions on study entry. This study type effect should be accounted for in future evaluations of communication and patient satisfaction. The data also support the fact that cancer patients have a desire for and ability to understand rather detailed and comprehensive treatment information.

Adult↗
PubMed2003

Acute tumor lysis syndrome in solid tumors--a case report and review of the literature.

PURPOSE: Tumor lysis syndrome (TLS) is a potential complication in cancer therapy. It may occur in highly sensitive tumors, especially in childhood cancers and acute leukemias, whereas it is rare in the treatment of adult solid tumors. TLS is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia following massive lysis of malignant cells. Complications include acute renal failure and metabolic acidosis. We report the first case of TLS during chemotherapy in a patient with metastatic medulloblastoma, together with a review of the literature regarding the occurrence of TLS in patients with solid tumors. METHODS: Data regarding clinical and biochemical parameters were extracted from the actual patients' files. Reports of TLS in the English language literature up to 2002 were identified by searching Medline. RESULTS: A 23-year old male with metastatic medulloblastoma received chemotherapy with cisplatin and etoposide due to massive extracerebral manifestations including metastases to the liver, mediastinal lymph nodes and bone marrow metastases. The patient developed classical signs of TLS on the second day of chemotherapy, including acute renal failure. A 17-fold increase in plasma LDH up to 87608 U/l was observed together with a 4-fold increase in plasma creatinine. The patient was treated with aggressive hydration, allopurinol and repeated hemodialysis. During the following days the patient improved and the biochemical markers all returned to normal. REVIEW. Reviewing the literature, a total of 45 patients with solid tumors who developed TLS have been reported. Most of the patients presented with metastatic, therapy-sensitive disease. Although preventable in practically 100% of patients, TLS is a potentially fatal complication, and in this material the mortality rate was one in three. Risk factors included increased LDH, hyperuricemia and pretreatment azotemia. CONCLUSIONS: TLS is only rarely associated with treatment of solid tumors. Precautions should be taken to avoid this potentially fatal complication in (chemo)therapy of solid tumors, especially in therapy-sensitive tumors presenting with bulky, metastatic disease and preexisting risk factors, including azotemia, elevated LDH and hyperuricemia. Prophylactic treatment to avoid TLS includes allopurinol, hydration prior to treatment and alkalization of the urine. Urate oxidase (rasburicase) is now beginning to replace allopurinol as a more effective way of reducing hyperuricemia and thereby the risk of TLS.

Adult↗
PubMed2001

Maxi K+ channels co-localised with CFTR in the apical membrane of an exocrine gland acinus: possible involvement in secretion.

The primary secretion formed in various exocrine glands has a [K+] 2-5 times that of plasma. In this study we measured the transepithelial flux of 36Cl-, 22Na+ and 42K+ across the frog skin and applied the single-channel patch-clamp technique to the apical membrane of frog skin gland acini to investigate the pathway taken by K+ secreted by the glands. Transepithelial K+ secretion was active and was driven by a larger force than the secretion of Na+. When driving Na+ through the epithelium by clamping the transepithelial potential to 100 mV (apical solution reference), blockers of cellular secretion (apical 5-nitro-2-(3-phenylpropylamino)benzoate or basolateral quinine or furosemide) decreased K+ secretion but left Na+ secretion unaffected. We conclude that K+ follows a transcellular pathway across the epithelium. Patch-clamp analysis of the apical membrane of microdissected gland acini revealed a population of voltage- and calcium-activated K+ channels of the maxi K+ type. In cell-attached patches these channels were activated by membrane potential depolarisation or exposure to prostaglandin E2 and had a permeability of 3.6 +/- 0.3 x 10(-13) cm3 s-1, giving a calculated conductance of 170 pS with 125 mM K+ on both sides of the membrane. In inside-out patches the channels were activated by increasing intracellular [Ca2+] from 10(-7) to 10(-6) M and were blocked by Ba2+ added to the cytoplasmic side. Exposure of inside-out patches containing the maxi K+ channel to ATP on the inside activated cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels, confirming that both channels are co-localised to the apical membrane. We interpret these findings in terms of a model where transepithelial NaCl secretion can be supported in part by an apical K+ conductance.

Amiloride↗
PubMed2000

Deletion of the S3-S4 linker in the Shaker potassium channel reveals two quenching groups near the outside of S4.

When attached outside the voltage-sensing S4 segment of the Shaker potassium channel, the fluorescent probe tetramethylrhodamine (TMRM) undergoes voltage-dependent fluorescence changes (DeltaF) due to differential interaction with a pH-titratable external protein-lined vestibule (Cha, A., and F. Bezanilla. 1998. J. Gen. Physiol. 112:391-408.). We attached TMRM at the same sites [corresponding to M356C and A359C in the wild-type (wt) channel] in a deletion mutant of Shaker where all but the five amino acids closest to S4 had been removed from the S3-S4 linker. In the deletion mutant, the maximal DeltaF/F seen was diminished 10-fold, and the DeltaF at M356C became pH independent, suggesting that the protein-lined vestibule is made up in large part by the S3-S4 linker. The residual DeltaF showed that the probe still interacted with two putative quenching groups near the S4 segment. One group was detected by M356C-TMRM (located outside of S3 in the deletion mutant) and reported on deactivation gating charge movement when applying hyperpolarizing voltage steps from a holding potential of 0 mV. During activating voltage steps from a holding potential of -90 mV, the fluorescence lagged considerably behind the movement of gating charge over a range of potentials. Another putative quenching group was seen by probes attached closer to the S4 and caused a DeltaF at extreme hyperpolarizations (more negative than -90 mV) only. A signal from the interaction with this group in the wt S3-S4 linker channel (at L361C) correlated with gating charge moving in the hyperpolarized part of the Q-V curve. Probe attached at A359C in the deletion mutant and at L361C in wt channel showed a biphasic DeltaF as the probe oscillated between the two groups, revealing that there is a transient state of the voltage sensor in between, where the probe has maximal fluorescence. We conclude that the voltage sensor undergoes two distinct conformational changes as seen from probes attached outside the S4 segment.

Animals↗
PubMed2000

A mathematical model of solute coupled water transport in toad intestine incorporating recirculation of the actively transported solute.

A mathematical model of an absorbing leaky epithelium is developed for analysis of solute coupled water transport. The non-charged driving solute diffuses into cells and is pumped from cells into the lateral intercellular space (lis). All membranes contain water channels with the solute passing those of tight junction and interspace basement membrane by convection-diffusion. With solute permeability of paracellular pathway large relative to paracellular water flow, the paracellular flux ratio of the solute (influx/outflux) is small (2-4) in agreement with experiments. The virtual solute concentration of fluid emerging from lis is then significantly larger than the concentration in lis. Thus, in absence of external driving forces the model generates isotonic transport provided a component of the solute flux emerging downstream lis is taken up by cells through the serosal membrane and pumped back into lis, i.e., the solute would have to be recirculated. With input variables from toad intestine (Nedergaard, S., E.H. Larsen, and H.H. Ussing, J. Membr. Biol. 168:241-251), computations predict that 60-80% of the pumped flux stems from serosal bath in agreement with the experimental estimate of the recirculation flux. Robust solutions are obtained with realistic concentrations and pressures of lis, and with the following features. Rate of fluid absorption is governed by the solute permeability of mucosal membrane. Maximum fluid flow is governed by density of pumps on lis-membranes. Energetic efficiency increases with hydraulic conductance of the pathway carrying water from mucosal solution into lis. Uphill water transport is accomplished, but with high hydraulic conductance of cell membranes strength of transport is obscured by water flow through cells. Anomalous solvent drag occurs when back flux of water through cells exceeds inward water flux between cells. Molecules moving along the paracellular pathway are driven by a translateral flow of water, i.e., the model generates pseudo-solvent drag. The associated flux-ratio equation is derived.

Animals↗
PubMed1999

Membrane potential and conductance of frog skin gland acinar cells in resting conditions and during stimulation with agonists of macroscopic secretion.

Frog skin glands were stripped of connective tissue and investigated using the nystatin-permeabilized whole-cell patch-clamp configuration. The membrane potential in unstimulated acinar cells was -69.5+/-0.7 mV, and the conductance was dominated by K+, based on ion substitution experiments. The cells were electrically coupled through heptanol- and halothane-sensitive gap junctions. During application of gap junction blockers, the whole-cell current/voltage relationship displayed strong outward rectification. Outward currents were blocked by barium. Stimulation by agonists known to cause increases in either cytosolic cAMP ([cAMP]c) (isoproterenol, prostaglandin E2, both at 2 microM) or free cellular Ca2+ concentration ([Ca2+]c) (noradrenaline, 10 microM, added with propranolol, 5 microM; carbachol, 100 microM) in the frog skin glands caused reversible depolarization: by 34+/-3 mV, 36+/-3 mV, 25+/-3 mV (plateau-phase), and 20+/-3 mV, respectively. Ion substitution experiments showed that stimulation through either pathway (cAMP or Ca2+) resulted in the activation of a Cl- conductance. Application of noradrenaline or adrenaline resulted in a faster depolarization (rates 22 mV/s, 26 mV/s) than stimulation by isoproterenol or prostaglandin E2 (5.6-5.7 mV/s). Cells that were depolarized by exposure to isoproterenol or prostaglandin E2 partially repolarized when stimulated by noradrenaline. The repolarization was blocked by Ba2+ (5 mM) or prazosine (1 microM), consistent with the activation of Ca(2+)-dependent K+ channels via alpha1-adrenergic receptors. We conclude that in the frog skin gland both Ca(2+)-dependent and cAMP-dependent Cl- channels are present in the apical membrane. Increases in free [Ca2+]c in the cAMP-stimulated gland results in the activation of K+ channels, thereby increasing the driving force for Cl- exit.

Adrenergic alpha-Agonists↗
PubMed1999

Small bowel metastases in non-small cell lung cancer.

A case report of stage I adenocarcinoma of the lung in a 43-year-old female with recurrence in the small bowel and liver 11 months after pneumonectomy is presented. In addition, a cohort of 733 patients with non-small cell lung cancer (NSCLC) in all pretreatment stages (stages I-IV) with a total of 218 autopsies are evaluated, and the literature on the topic is reviewed, in order to define the frequency of metastases from NSCLC to the small bowel. There were 10 cases with and 208 cases without small bowel involvement among 218 consecutive autopsies (autopsy rate, 30%,). The frequency of small bowel involvement was 4.6% (95%, confidence interval, 2.2-8.3%), and all were in patients with adenocarcinoma of the lung. All patients with small bowel involvement at autopsy had also other concurrent metastatic sites as well and the following were the most frequent: adrenals (90%, of cases), mediastinal lymph nodes (80%), liver (70%), pleura (60%), contralateral lung (60%), bones (60%), and brain (50%). Significantly more metastatic sites were observed in patients with than without small bowel involvement, both totally (P = 0.0001) and with respect to number of extrathoracic (P = 0.0001) and intrathoracic (P = 0.01) metastatic sites. In conclusion, small bowel involvement in NSCLC is relatively infrequent. As a unique finding, over-representation of patients with poorly differentiated tumors (P = 0.03) and patients having solid carcinoma with mucus formation after histologic subtyping (P = 0.04) among cases with small bowel involvement was observed. This indicates, that small bowel metastases is an epiphenomonen of NSCLC tumors with certain biological characteristics, although as yet undiscovered, which leads to a high metastatic potential. If such biological characteristics could be identified, they may be used in the selection of treatment options for individual patients, e.g. indicating a need for adjuvant or neoadjuvant chemotherapy in addition to surgery in resectable or marginally resectable NCSLC patients.

Adult↗
PubMed1999

Paclitaxel, gemcitabine, and cisplatin in non-resectable non-small-cell lung cancer.

BACKGROUND: Paclitaxel, gemcitabine, and cisplatin are each active in non-small-cell lung cancer (NSCLC), and with different modes of action. Hence, a phase II study combining these drugs were conducted. PATIENTS AND METHODS: Treatment was paclitaxel 110 mg/m2 and cisplatin 60 mg/m2 day 1 and 15, with gemcitabine 800 mg/m2 day 1, 8, and 15, every four weeks. Patients had previously untreated NSCLC, measurable disease, age 18-70 years, performance status < or = 2, and no brain metastases. RESULTS: Among 49 patients, 6 (group 1) received chemotherapy as described above, while 43 patients (group 2) did not receive gemcitabine day 8. In group 1, all experienced grade 4 neutropenia and four achieved a partial response (67%). In group 2, neutropenia grade 4 occurred in 58%, with one episode of febrile neutropenia and no toxic death. No other grade 4 toxicities occurred, while grade 3 toxicity occurred with respect to thrombocytopenia (9%), nausea/vomiting (12%), neurotoxicity (12%), and nephrotoxicity (7%). There were 3 complete and 20 partial responses (response rate 54%, 95% confidence limits 38%-69%), median response duration 29 weeks (range 10-66+), median time to progression 28 weeks (range 4-66+), median survival 46 weeks (4-89+) and one-year survival rate 42%. CONCLUSION: This regimen of paclitaxel, gemcitabine, and cisplatin has neutropenia as dose limiting toxicity, but septicemic episodes were rare and toxic death did not occur. Other grade 4 toxicities than neutropenia did not occur. The regimen appears safe and with a noteworthy activity both in terms of response rate, time to progression, and survival.

Adult↗
PubMed1999

Phase II study of gemcitabine and vindesine in patients with previously untreated non-resectable non-small-cell lung cancer.

Because both vindesine and gemcitabine are active drugs in advanced non-small-cell lung cancer (NSCLC), with different modes of action and only partly overlapping toxicity, a phase II study was performed. Gemcitabine 1000 mg m(-2) was given on days 1, 8 and 15 every 4 weeks, while vindesine 3 mg m(-2) was administered weekly for 7 weeks, then every 2 weeks. A total of 42 patients with nonresectable NSCLC were included. The median age of patients was 56 years; 57% were men, 52% had adenocarcinoma, 31% squamous cell carcinoma and 17% had large-cell carcinoma. The performance status ranged from 0 to 2 with 83% in performance status 1. The majority (55%) had stage IV disease, while 40% had stage III B and 5% stage III A disease. WHO grade 3-4 leucopenia occurred in five patients (12%) and 9% had grade 4 neutropenia. Thrombocytopenia grade 3-4 was observed in six patients (15%). There were no septic death or bleeding episodes. One patient had a transient WHO grade 4 increase in bilirubin, and four patients had a decrease in glomerular filtration rate below the normal limit; one of these patients developed a non-reversible renal insufficiency. Ten patients (24%) complained of dyspnoea of uncertain mechanism, possibly involving bronchoconstriction. There were one complete and seven partial responses among 40 assessable patients (20%, 95% confidence limits 9-36%). Median response duration was 31 weeks (range 11-83 weeks) and median survival time 31 weeks (range 2-171 weeks). The current combination of gemcitabine and vindesine does not appear to be promising for further examination because of the toxicity and somewhat disappointing activity.

Adult↗
PubMed1999

Metastatic pattern in non-resectable non-small cell lung cancer.

This study describes the metastatic pattern at autopsy in patients with non-resectable non-small cell lung cancer (NSCLC) and evaluates the impact of various pretreatment variables and treatment outcomes on the metastatic spread. In eight phase II chemotherapy trials from 1985 through 1993, 337 patients were treated and 51 autopsies were performed (autopsy rate 15%). The male/female ratio was 31/20, median age 56 years (range 36-71), response rate to chemotherapy 8%, and median survival 88 days (range 3-899). Histologic types included adenocarcinoma, 31 cases (60%), squamous cell carcinoma, 9 cases (18%), large cell carcinoma, 9 cases (18%), and unclassified NSCLC, 2 cases (4%). Patients who were autopsied had a shorter median survival than patients without autopsy (p = 0.002, log-rank test). Most commonly involved metastatic sites found at autopsy were mediastinal lymph nodes (84%), pleura (51%), liver (47%), bone (34%), brain (32%), pericardium (29%), adrenals (29%). The median number of involved organs was 5 (range 1-16), with a median of 3 intrathoracic sites (range 1-8) and 2 extrathoracic sites (range 0-11). Patients who initially had metastatic NSCLC also had significantly more metastatic sites at autopsy both extrathoracic (p = 0.004) and totally (p = 0.03) compared to patients with locally advanced disease. No other relation to pretreatment variables was found.

Adult↗
PubMed1998

[The role of tumor marker CA 125 in the treatment of ovarian cancer].

Among the gynaecological malignancies in Denmark, ovarian cancer still has the highest mortality. At diagnosis, the majority of the patients show disseminated diseases and are treated with a combination of surgery and chemotherapy. At the conclusion of treatment and at later control examinations, the patients are evaluated by pelvic examination, ultrasound scans, CT-scanning, determination of the tumor-marker CA 125 and explorative laparotomy ("second look operation"). Based on studies of the literature the utility of CA 125 as a marker for the activity of the disease in patients with ovarian cancer during and after treatment is evaluated. It is concluded that CA 125 levels above 35 E/ml are seen in 85% of women with ovarian cancer. CA 125 as a sole parameter cannot be used for the screening of women for ovarian cancer, since high CA 125 values may be seen in conditions other than ovarian cancer. Normalisation of CA 125 values is a condition but not a guarantee for regression of the disease, since patients with a normal CA 125 may have progression of the disease. A rise in CA 125 during or after treatment, however, is almost always associated with progression of the disease.

Biomarkers, Tumor↗
PubMed1998

Primitive neuroectodermal tumor (PNET) of the uterine cavity.

The occurrence of primitive neuroectodermal tumors located in the uterus is extremely rare. Eight cases have been described in the literature, and with the addition of this ninth case, we summarize treatment and outcome of PNET located in the uterine cavity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Patch clamp on the luminal membrane of exocrine gland acini from frog skin (Rana esculenta) reveals the presence of cystic fibrosis transmembrane conductance regulator-like Cl- channels activated by cyclic AMP.

Chloride channels in the luminal membrane of exocrine gland acini from frog skin (Rana esculenta) constituted a single homogeneous population. In cell-attached patches, channels activated upon exposure to isoproterenol, forskolin, or dibutyryl-cAMP and isobutyl-1-methyl-xanthine rectified in the outward direction with a conductance of 10.0 +/- 0.4 pS for outgoing currents. Channels in stimulated cells reversed at 0 mV applied potential, whereas channels in unstimulated cells reversed at depolarized potentials (28.1 +/- 6.7 mV), indicating that Cl- was above electrochemical equilibrium in unstimulated, but not in stimulated, cells. In excised inside-out patches with 25 mM Cl- on the inside, activity of small (8-pS) linear Cl--selective channels was dependent upon bath ATP (1.5 mM) and increased upon exposure to cAMP-dependent protein kinase. The channels displayed a single substate, located just below 2/3 of the full channel amplitude. Halide selectivity was identified as PBr > PI > PCl from the Goldman equation; however, the conductance sequence when either halide was permeating the channel was GCl > GBr >> GI. In inside-out patches, the channels were blocked reversibly by 5-nitro-2-(3-phenylpropylamino)benzoic acid, glibenclamide, and diphenylamine-2-carboxylic acid, whereas 4, 4-diisothiocyanatostilbene-2,2-disulfonic acid blocked channel activity completely and irreversibly. Single-channel kinetics revealed one open state (mean lifetime = 158 +/- 72 ms) and two closed states (lifetimes: 12 +/- 4 and 224 +/- 31 ms, respectively). Power density spectra had a double-Lorentzian form with corner frequencies 0.85 +/- 0.11 and 27.9 +/- 2.9 Hz, respectively. These channels are considered homologous to the cystic fibrosis transmembrane conductance regulator Cl- channel, which has been localized to the submucosal skin glands in Xenopus by immunohistochemistry (Engelhardt, J.F., S.S. Smith, E. Allen, J.R. Yankaskas, D.C. Dawson, and J.M. Wilson. 1994. Am. J. Physiol. 267: C491-C500) and, when stimulated by cAMP-dependent phosphorylation, are suggested to function in chloride secretion.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Metastatic pattern at autopsy in non-resectable adenocarcinoma of the lung--a study from a cohort of 259 consecutive patients treated with chemotherapy.

A cohort of 259 consecutive patients with non-resectable adenocarcinoma of the lung (ACL) received chemotherapy and were followed until death with 124 cases examined by autopsy (autopsy rate 48%). Metastatic sites were identified and the following localisations were affected in 40% or more of patients post mortem: lungs, mediastinal lymph nodes, liver, pleura, adrenals, brain, and bones. Significant more metastatic sites were observed in patients who responded to the chemotherapy compared with non-responders (p = 0.04), in patients aged below the median of 58 years compared with older patients (p = 0.002), and, as expected, in patients with initial extensive disease compared with limited disease (p = 0.03). In contrast, no differences in metastatic pattern at autopsy could be detected with regard to other variables, such as initial TNM-stages, degree of histological differentiation, histologic subtypes, performance status, or LDH.

Adenocarcinoma↗
PubMed1997

Development of syndrome of inappropriate secretion of antidiuretic hormone during progression of metastatic breast cancer.

A patient who developed syndrome of inappropriate secretion of antidiuretic hormone (SIADH) during progression of metastatic breast cancer is described. The classic criteria for SIADH as defined by Bartter and Schwartz were fulfilled and conditions other than malignant disease were excluded as causes of the syndrome. To the knowledge of the authors SIADH has never been reported to develop during the course of malignant disease in a patient with metastatic breast cancer. It should be borne in mind that SIADH may occur in patients with malignant disease and hyponatraemia, even in the absence of small-cell lung cancer, which is the classic tumour type to develop SIADH.

Antineoplastic Combined Chemotherapy Protocols↗