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Biomedical subjects

S M Allen

Publications and source records attributed to S M Allen.

48 records · Page 3Linked to original sources

Assessment of the response to chemotherapy in oesophageal cancer.

Thirty-eight patients with localised oesophageal carcinoma have been studied by computed tomography (CT) and barium swallow before and after preoperative chemotherapy and the results correlated with the pathological findings in the resected specimen. Overall 48% of patients showed a complete or partial response to chemotherapy on CT, compared with 50% on barium and 94% on pathological examination. This study highlights deficiencies in CT scanning and barium swallow as methods of assessing the regression of tumor bulk following chemotherapy for oesophageal carcinoma. We suggest that strict and specific criteria will have to be laid down before the results of chemotherapy in this disease can be reliably and accurately evaluated.

Aged↗

A phase II study of 5-fluorouracil, adriamycin and mitomycin-C in adenocarcinoma of the oesophagus.

We have evaluated the effect of 5-fluorouracil 600 mg/m2, doxorubicin ('Adriamycin') 40 mg/m2, and Mitomycin-C 4 mg/m2 (FAM) in two groups of patients with adenocarcinoma of the oesophagus, as either a preoperative or primary treatment. Response was assessed by barium swallow, CT scan, and measurement of metastases where present. Toxicity was as reported for FAM in gastric cancer. In the operated group 8 of 22 patients (36%) showed a partial response following two courses of FAM. Resection was completed in 20 patients, with six hospital deaths (30%). Of the 14 patients who were discharged from hospital, 8 have died (median 8 months) and 6 are alive at 12 to 27 months, with known recurrence in 1. In the non-operated group 6 of 17 patients (35%) showed a response, one complete, following one to six (mean 4.2) courses of FAM. Fifteen patients have died (median 5 months), and 2 are alive and free from disease at 12 and 17 months. Neoadjuvant therapy with FAM in adenocarcinoma of the oesophagus offers no advantage over surgery alone, although with inoperable disease FAM may be of use in palliation.

Adenocarcinoma↗

Surgical treatment of massive hydrothorax complicating continuous ambulatory peritoneal dialysis.

Acute hydrothorax is a well-recognized complication of continuous ambulatory peritoneal dialysis and is often regarded as a contraindication to its use. We report three cases treated by surgical closure of a communication between the peritoneal and pleural cavities enabling CAPD to continue successfully. This is a simple, safe and effective procedure which merits wider use as an alternative to transferring the patient to permanent hemodialysis.

Aged↗

A proposed mouse model for acute epididymitis provoked by genital serovar E, Chlamydia trachomatis.

This study was conducted to determine the efficacy of the male mouse as a model for epididymitis caused by human genital serovar E, Chlamydia trachomatis. C. trachomatis was reisolated from all tissues removed on Days 3, 5, and 7 post inoculation (pi). Although some infected epididymides removed on Days 10, 14, and 21 pi were positive, control tissues remained negative. Histopathology of tissues showed a heavy, mixed inflammatory infiltrate consisting of polymorphonuclear cells and lymphocytes. Serum antibody to C. trachomatis was detected in the infected mice only (titer greater than or equal to 1:32). Chlamydial inclusions and individual elementary bodies were confirmed by immunofluorescent and immunoperoxidase staining up to Day 7 pi. These data show that the male mouse is susceptible to C. trachomatis infection and is appropriate for studies dealing with the effect of C. trachomatis on male fertility.

Acute Disease↗

Hip fractures in healthy patients: operative delay versus prognosis.

One hundred and forty five women who had undergone hemiarthroplasty for a subcapital fracture of the femoral neck but who were otherwise fit were studied to determine whether undue delay between injury and operation influenced their social circumstances three months after surgery. The median delay for those patients who showed good rehabilitation at three months was 29 hours, but for those who showed poor rehabilitation it was 57 hours. This difference was significant. It is suggested that a subcapital fracture in an otherwise fit elderly patient should therefore be regarded as a surgical emergency.

Aged↗

Importance of low serum vitamin B12 and red cell folate concentrations in elderly hospital inpatients.

To determine the functional importance of the low B12 and red cell folate concentrations repeatedly observed in the elderly 200 consecutive patients admitted to a geriatric unit were studied. Forty six of the patients had low serum concentrations of B12 (15), red cell folate (26), or both (five). Serum B12 and red cell folate concentrations correlated with mean cell volume, and serum B12 correlated with the neutrophil lobe count. Bone marrow deoxyuridine suppression was abnormal in 35% of the patients with low vitamin concentrations, but 55% of those with abnormal deoxyuridine suppression had morphologically normal bone marrow, and 73% had a normal mean cell volume. In patients with low vitamin values the deoxyuridine suppressed value correlated with the haemoglobin concentration and neutrophil lobe count. Thus synthesis of thymidylate was impaired by vitamin B12 or folate deficiency in at least 8% of newly admitted elderly patients, many of whom had normal blood counts despite the biochemical disturbance affecting haemopoiesis. A nutritionally depleted diet may have been responsible for many of the low vitamin values.

Aged↗

Fall in vital capacity with posture.

In a study of 147 subjects (50 normals, 50 with obstructive, and 47 with restrictive lung function), the mean reduction in forced vital capacity from standing to supine (delta FVC) was 7.5% (SD +/- 5.7), 11.2% (+/- 13.4), and 8.2% (+/- 7.7) respectively, with no significant difference between groups. The respective 95% upper confidence limits were 19%, 38% and 24%. We conclude that delta FVC greater than 25% associated with normal or restrictive lung function or greater than 35% associated with airways obstruction should be an indication for further study of diaphragm function.

Adult↗

Type II regulatory subunit of cAMP-dependent protein kinase. Phosphorylation by casein kinase II at a site that is also phosphorylated in vivo.

A study of the phosphorylated sites on the regulatory subunit of type II cyclic AMP-dependent protein kinase is described. The site of autophosphorylation, previously reported (Takio, K., Walsh, K. A., Neurath, H., Smith, S. B., Krebs, E. G., and Titani, K. (1980) FEBS Lett. 114, 83-88), is found to contain the only residue phosphorylated by the catalytic subunit. Endogenous protein-bound phosphate, present at a second site, is observed in the NH2-terminal region of purified type II regulatory subunit. A serine residue in this same domain of type II regulatory subunit is shown to be phosphorylated in vitro by casein kinase II. The stoichiometry of phosphate incorporation by casein kinase II indicates a single site of phosphorylation that is equivalent to the site containing the endogenous phosphate. The apparent Km and Vmax of casein kinase II for the phosphorylation of purified type II regulatory subunit containing 0.55 molar equivalents of endogenous phosphate are 36 microM and 3.5 mumol/min/mg, respectively. Phosphatase treatment of type II regulatory subunit decreased the determined Km to 13 microM but does not change the Vmax consistent with the suggestion that casein kinase II is phosphorylating a site partially occupied by endogenous phosphate. Comparison of peptide maps of type II regulatory subunit phosphorylated in vitro by casein kinase II with in vivo modified type II regulatory subunit indicates that the site modified in vitro is also phosphorylated in vivo.

Amino Acid Sequence↗

Effect of phosphorylation on the regulatory subunit of the type I cAMP-dependent protein kinase.

The regulatory subunit of the type I cAMP-dependent protein kinase (RI), isolated from bovine or rat skeletal muscle, can be phosphorylated both in vitro (Geahlen, R. L., and Krebs, E. G. (1980) J. Biol. Chem. 255, 1164-1169) and in vivo (Geahlen, R. L., and Krebs, E. G. (1980) J. Biol. Chem. 255, 9375-9379). The effects of each modification on the ability of RI to associate with the catalytic subunit (C) and with cAMP are compared. The phosphorylation of bovine RI in vitro by cGMP-dependent protein kinase results in a loss of inhibitory activity toward C and in the loss of one of two cAMP binding sites per RI monomer. Inhibitory activity can be regained upon removal of the phosphate with potato acid phosphatase. Similar effects are not observed for the subunits phosphorylated in vivo. A comparison of unmodified bovine RI with RI modified in vivo reveals no differences in their interactions with either C or cAMP. Dephosphorylation of purified rat RI also does not affect its association with C or subsequent activation by cAMP. Dephosphorylated rat RI is not a substrate for C but can be slowly phosphorylated by cGMP-dependent protein kinase. The phosphorylation of RI in isolated rat soleus muscles is not inhibited by cycloheximide, ruling out the possibility that only nascent polypeptide chains are substrates for phosphorylation in vivo.

Acid Phosphatase↗