A phase I study of a combination of allopurinol, 5-fluorouracil and leucovorin followed by hydroxyurea in patients with advanced gastrointestinal and breast cancer

Twenty patients with advanced carcinomas of the colorectum, pancreas, stomach, and breast were enrolled in a Phase I study of a sequential administration of 5-fluorouracil-leucovorin (FU-LV) combination followed by hydroxyurea (HU) with allopurinol protection (HALF regimen). As a weekly regimen for 6 weeks, followed by a rest period of 2 weeks, FU was administered intravenously (i.v.) during infusion of a 2-hour i.v. infusion of LV at a dose of 500 mg/m2. Six hours following the FU-LV combination, HU (1 gm/m2) was administered orally. Allopurinol (300 mg every 8 hours, orally) was given the day before and on the day of the administration of the FU-LV combination. The starting dose of FU was 300 mg/m2, with escalations to 900 mg/m2. Mucositis, diarrhea, and hematologic toxicities were mild and sporadic with FU doses up to 750 mg/m2 and occurred in patients who had received prior treatment with FU and/or radiotherapy. Dose-limiting neurocerebellar toxicity was observed in 2 out of 6 patients who received a FU dose of 900 mg/m2. Three additional patients experienced moderate neuromotor toxicity at this dose level. Among 17 patients evaluable for response, partial responses were seen in 3 of the 9 patients with colorectal cancer, 1 of the 3 patients each with carcinoma of breast and pancreas. Three of the 5 responses occurred in patients who had received prior treatment with FU and/or radiation therapy. An FU dose of 750 mg/m2 is recommended for a Phase II trial of the HALF regimen.     

A micro-perfusion chamber for single-cell fluorescence measurements

A versatile closed micro-perfusion chamber designed for single-cell fluorescence measurements under maximum microscopic magnification is described. Glass coverslips with adherent cells can be attached to the top or bottom of the chamber, depending on whether an inverted or an upright microscope is used. Eight conical holes drilled in the side of the chamber serve for the insertion of plugs with attachments for perfusion, rapid injection of small amounts of reagents, temperature measurements or for heating the interior of the chamber. Materials used in the construction of the chamber are non-toxic and resistant to standard sterilization procedures. Perfusion and temperature properties of the chamber are described. Single cell fluorescence measurements are presented in human monocyte-derived macrophages in which NAD(P)H and intracellular calcium are measured.     

Quantitative neuropathological study of Alzheimer-type pathology in the hippocampus: comparison of senile dementia of Alzheimer type, senile dementia of Lewy body type, Parkinson's disease and non-demented elderly control patients.

A Lewy body dementing syndrome in the elderly has been recently described and designated senile dementia of Lewy body type (SDLT) on the basis of a distinct clinicopathological profile. The pathological changes seen in SDLT include the presence of cortical Lewy bodies (LB) frequently, but not invariably, associated with senile plaque (SP) formation. Whilst neocortical neurofibrillary tangles (NFT) are sparse or absent, a proportion of these cases show involvement of the temporal archicortex by lesions comprising Alzheimer-type pathology (ATP, i.e. NFT, SP and granulovacuolar degeneration [GVD]). Thus the relationship between SDLT and senile dementia of Alzheimer type (SDAT) is complex and controversial. In this study quantitative neuropathology was used to compare the intensity and distribution of ATP in the hippocampus and entorhinal cortex of 53 patients from 3 disease groups (SDLT, SDAT, Parkinson's disease (PD)) and a group of neurologically and mentally normal elderly control patients. For most brain areas examined the extent of ATP between the patient groups followed the trend SDAT greater than SDLT greater than PD greater than control. Statistical comparison of these groups revealed significant differences between the mean densities of NFT, SP and GVD although individual cases showed considerable variability. These results confirm additional pathological differences between SDAT and SDLT regarding the intensity of involvement of the temporal archicortex by ATP. Many patients with Lewy body disorders (LBdis) show a predisposition to develop ATP albeit in a more restricted distribution (e.g. low or absent neocortical NFT) and at lower densities than is found in SDAT. Some cases of SDLT show minimal SP and NFT formation in both neocortex and archicortex supporting previously published data distinguishing this group from Alzheimer's disease.     

Toxic reaction to inhaled paint fumes

An acute confusional state was observed to follow heavy exposure to polyurethane gloss paint fumes in a previously healthy 60 year old man. This state remitted over a 3-day period, but was followed by transient bone marrow suppression and evidence of liver cell damage. The corroborated absence of other toxins and the temporal association of exposure to paint fumes suggest that a volatile paint component was responsible. White spirit is the major volatile solvent in polyurethane gloss paint. Ingestion of related aliphatic hydrocarbons has been reported to cause nausea, drowsiness and hepatotoxicity, but these symptoms have not previously been documented following excessive inadvertent inhalation of paint fumes.     

A case-control study of twin pairs discordant for Parkinson's disease: a search for environmental risk factors

A previous study of twins with Parkinson's disease (PD) revealed low concordance, suggesting that genetic factors play a minor role in the etiology of PD. To identify possible environmental determinants of PD while maximally controlling for hereditary factors, 31 monozygotic twin pairs discordant for PD were interviewed by telephone. Information about possible risk factors was obtained from systematic and uniform interviews with cases and controls. The only statistically significant result was less cigarette smoking by PD patients (p less than 0.05). Thirteen dizygotic discordant twin pairs were evaluated with the same techniques, but there were no statistically significant differences between affected and unaffected twins.     

Kommentar zu den Leitlinien (2017) der ESC/EACTS zum Management von Herzklappenerkrankungen

Zeitschrift für Herz-,Thorax- und Gefäßchirurgie - Seit der letzten Herausgabe der Leitlinien zur Behandlung von Klappenfehlern durch die European Society of Cardiology (ESC) und die...     

The Effects of Positive End-Expiratory Pressure at Different Levels on Postoperative Respiration Parameters in Patients Undergoing Laparoscopic Cholecystectomy

Purpose/Aim of the study: We investigated the effects of different positive end-expiratory pressure (PEEP) levels on postoperative respiration parameters in patients undergoing laparoscopic cholecystectomy. Materials and Methods: One hundred and five consecutive patients were randomly divided to three groups (n = 35, for each group). Group I did not receive PEEP whereas group II received PEEP as 5 cmH₂O and group III received PEEP as 8 cm H₂O. Measurements with spirometer were taken 1 hour before the operation (T₁) and, 1 (T₂), 6 (T₃), and 24 hours (T₄) after extubation by an anesthetist. Forced expiratory volume (FEV₁), forced vital capacity (FVC), and peak expiratory flow (PEF) were recorded. Results: Group I had higher FVC values measured at T₂ time point compared with other groups (p < 0.05, for both groups). There was a statistically significant difference between group I and group III in terms of the FVC values measured at T₃ and T₄ time points (p = 0.05 and p < 0.05, retrospectively). A statistical difference was found between group I and group II in terms of FEV₁ measured at T₂ time point (p < 0.05). Group I had higher FEV₁ values measured at T₃ and T₄ time points compared to group III (p = 0.05, P<0.05; respectively). Group III had lower PEF values measured at T₄ time point compared to group I and II (p < 0.05). Conclusions: We concluded that PEEP with 5 or 8 cmH₂O has negative effects on lung function tests measured with spirometer during postoperative 1^st, 6^th, and 24^th hours in patients underwent elective laparoscopic cholecystectomy.     

Glucocorticoids are not always deleterious for bone

A 23‐year‐old man with the rare sclerosing bone disorder van Buchem disease presented with progressively worsening headaches that eventually became persistent and associated with papilledema. Increased intracranial pressure was diagnosed, and the patient had a ventriculoperitoneal drain inserted as well as simultaneously receiving treatment with prednisone. Before starting treatment, there was biochemical evidence for increased bone turnover and for steady increases in bone mineral density (BMD) at the spine and total hip despite the patient having reached his peak height of 197 cm at the age of 19 years. Treatment with prednisone for 2 years resulted in biochemical and histologic suppression of bone formation as well as of bone resorption and arrest of further bone accumulation. Our data suggest that glucocorticoids (GCs) may represent an attractive alternative to the high‐risk surgical approaches used in the management of patients with progressive sclerosing bone disorders. Our findings also suggest that whereas sclerostin may not be required for the action of GCs on bone formation, it may well be important for the action of GCs on bone resorption. The exact mechanism by which sclerostin may be involved in the regulation of bone resorption is as yet to be explored. © 2010 American Society for Bone and Mineral Research.