Biomedical subjects
C Gray
Publications and source records attributed to C Gray.
Acute appendicitis: CT and US correlation in 100 patients.
PURPOSE: To compare the accuracy of computed tomography (CT) and ultrasonography (US) in the diagnosis of acute appendicitis. MATERIALS AND METHODS: One hundred consecutive patients were examined with US and CT, and the results, independently reported, were correlated with surgical and histopathologic findings (69 patients) and data from other laboratory and clinical follow-up (31 patients). RESULTS: Fifty-four patients had acute appendicitis; 46 patients did not. Analysis of the data for CT and US, respectively, revealed sensitivity, 96% versus 76%; specificity, 89% versus 91%; accuracy, 94% versus 83%; positive predictive value, 96% versus 95%; and negative predictive value, 95% versus 76%. In the 46 patients without appendicitis, an alternative diagnosis was made with CT in 22 patients and with US in 15. CT scans showed abscesses and/or phlegmons in 28% of patients with appendicitis versus 17% at US. Results of CT and US were discordant in 20 patients; CT findings were correct in 17 and US findings in three. CONCLUSION: CT is more accurate than US in diagnosis of acute appendicitis.
Tumour kinetics in breast cancer.
In vivo bromodeoxyuridine was used to measure the 'bromo' labelling index (LI,%), the duration of the S-phase (Ts, hours) and the potential tumour doubling time (Tpot, days) in women with stages I-IV breast cancer. These were studied in relation to lymph node status, tumour size, histological grade, oestrogen receptor status (ER), ploidy and S-phase fraction (SPF). In our patients, a LI of 10%, a Tpot of 2 days or an SPF of 9-10.5% predicted aggressive breast cancer. The LI was significantly higher (5%) in ER-negative than in ER-positive (2%) tumours (P = 0.03). There was a trend towards increased DNA synthesis in cancers with an SPF over 10% (P = 0.08). ER-negative breast cancers over 2 cm in diameter had shorter median Tpots of 5.3 days (P = 0.02) and 8 days (P = 0.05) compared with smaller, ER-positive tumours. A trend towards faster growth rates was seen in lymph node-positive, high-SPF (> 10%) breast cancers. Tumour kinetics may have additional prognostic value in the selection of node-negative patients for adjuvant therapy.
Evidence that the Gh protein is a signal mediator from alpha 1-adrenoceptor to a phospholipase C. I. Identification of alpha 1-adrenoceptor-coupled Gh family and purification of Gh7 from bovine heart.
Our previous studies on alpha 1-adrenoceptor-mediated signaling suggested that Gh is a signal mediator. Gh consists of a 74-kDa GTP-binding alpha-subunit and a 50-kDa beta-subunit. Studies using the alpha 1-agonist-receptor-G-protein ternary complexes from various tissues and species revealed that the intensity (GTP-binding) of the [alpha-32P]GTP-labeled proteins resulting from activating the alpha 1-receptor was significantly attenuated by phentolamine. The molecular masses of GTP-binding proteins were 74 kDa in rat heart and liver, 77 kDa in dog heart, 78 kDa (Gh7 alpha) in bovine heart and liver, and 80 kDa in human heart. Supporting these observations, a specific antibody to Gh7 alpha not only recognized these GTP-binding proteins in the ternary complex preparations, but also co-immunoprecipitated alpha 1-adrenoceptors, indicating a tight association of these GTP-binding proteins with the alpha 1-adrenoceptor. These results also demonstrate that functional and structural similarities exist among these GTP-binding proteins. Additionally, one of the identified G-proteins (termed Gh7) was purified from bovine heart. Gh7 consisted of the 78-kDa GTP-binding protein and a 50-kDa protein.
Evidence that the Gh protein is a signal mediator from alpha 1-adrenoceptor to a phospholipase C. II. Purification and characterization of a Gh-coupled 69-kDa phospholipase C and reconstitution of alpha 1-adrenoceptor, Gh family, and phospholipase C.
Our studies on the alpha 1-adrenoceptor signaling have demonstrated that the Gh family is a signal mediator. We report here that a 69-kDa phospholipase C (PLC) is the effector in this signal pathway. The enzyme was isolated by dissociating a Gh7-PLC complex which was induced in the bovine liver membranes incubating with (-)-epinephrine and GTP. The enzyme displayed a marked preference hydrolysis for phosphatidylinositol 4,5-bisphosphate over other phosphatidylinositides at micromolar calcium. Reconstitution of PLC with the alpha 1-adrenoceptor and Gh (Gh7) into phospholipid vesicles resulted in a lowered Ca2+ requirement for the substrate hydrolysis in the presence of guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) when the receptor was activated with the alpha 1-agonist. The formation of inositol phosphate was hormone concentration dependent and reached maximal within 3 min which was faster than the formation in the presence of the alpha 1-antagonist. An Gh7 alpha antibody co-immunoprecipitated 80-85% of phospholipase C activity in the presence of GTP gamma S, but not in the presence of GDP or buffer, showing the association of PLC with the alpha-subunit of Gh family. Thus, our novel approaches to identify the effector involved in the alpha 1-adrenoceptor signaling, as well as the reconstitution studies, substantially demonstrate that the alpha 1-adrenoceptor-mediated transmembrane signaling involves the Gh family and a 69-kDa PLC.
Preoperative and postoperative combination chemotherapy for potentially resectable gastric carcinoma.
BACKGROUND: Median survival of patients with local-regional gastric carcinoma is 10 months. Resection of the primary tumor and regional lymph nodes, with tumor-free margins (curative resection), has been the most effective treatment for local-regional gastric carcinoma. However, median survival of patients with curative resection of gastric carcinoma is 24 months, and the 5-year survival rate is about 20%. A single institution pilot study has established the feasibility of administering two courses of chemotherapy preoperatively and three courses postoperatively. In another study, a 15% pathologically documented complete response (pathologic complete response) has been reported in unresectable gastric carcinoma treated with etoposide, doxorubicin, and cisplatin. PURPOSE: Our purpose was to increase the curative resection rate in potentially resectable gastric carcinoma and to delay or eliminate micrometastases and thus improve survival. We also evaluated clinical and pathologic response to chemotherapy. METHODS: Forty-eight previously untreated patients with potentially resectable gastric carcinoma received a chemotherapy regimen (EAP) consisting of etoposide (120 mg/m2 intravenously over a 2-hour period on days 4, 5, and 6), doxorubicin (20 mg/m2 as a 10-minute intravenous infusion on days 1 and 7), and cisplatin (40 mg/m2 as a 1-hour intravenous infusion on days 2 and 8). Patients received three courses of chemotherapy before resection, and responding patients received two courses postoperatively. Clinical and pathologic response rates, toxicity, patterns of treatment failure, and survival times were assessed. RESULTS: A median of three courses (range, 1-5) of preoperative therapy was administered; six (12%) of the 48 patients had clinical complete response, and nine (19%) had partial response. Forty-one (85%) underwent surgery; 37 (90%) of these 41 (77% of the 48 patients) had a curative resection. There were no pathologic complete responses. Median survival for all patients is 15.5 months (range, 2-29+ months). Therapy was discontinued because of the toxic effects in one patient before surgery and in six patients after surgery. Doses were reduced in 37 patients (77%), mainly because of hematologic toxicity. Nineteen (40%) were hospitalized because of toxic effects, including 15 patients who developed fever with neutropenia. Grade 3 or 4 nausea and vomiting occurred in 15 patients and grade 3 or 4 diarrhea in seven patients. One death was directly related to chemotherapy. CONCLUSIONS: These data support that administration of preoperative and postoperative chemotherapy for local-regional gastric carcinoma is feasible in a multi-institutional setting. Our findings demonstrate that this EAP regimen is modestly active but is associated with substantial toxicity. IMPLICATIONS: Use of preoperative chemotherapy in resectable gastric carcinoma merits further evaluation, but more effective drug regimens will be required before a controlled trial is initiated.
Sensory responses to passive hindlimb joint rotation in the cerebellar cortex of the cat.
We recorded from Purkinje cells in the anterior and posterior lobes of the cerebellar vermis in anesthetized cats during passive flexion and extension of the ipsilateral hind foot. Nearly 60% of the 302 cells recorded in lobules I-IV anterior and VII-IX posterior responded to this stimulus. In lobule V, generally considered to be the forelimb projection area, about a third of the 38 cells tested responded to hind foot movement. Cells in the anterior lobe typically exhibited different poststimulus patterns in response to foot flexion and extension while posterior cells usually had the same response to these stimuli. We also noted that cells recorded in the medial vermis (within 2.7 mm of the midline) generally had longer response latencies than cells recorded more laterally (2.7 mm of the midline) generally had longer response latencies than cells recorded more laterally (2.7-4.5 mm) in both lobes. The results illustrate a diffuse proprioceptive input to the cerebellar vermis which has different features in various cerebellar areas.
Canadian lawyer at Harvard a mainstay behind calls to change response to medical malpractice.
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US looks north for ideas as it struggles to control drug prices.
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In the US, the abortion issue will not die.
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Manufacturers, plastic surgeons draw fire at US forum on breast-implant issue.
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In the US, AIDS has become a "marginal" disease that affects thousands.
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US resistance to Canadian mammogram study not only about data.
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The incidence and size of gap junctions between the bone cells in rat calvaria.
Polyclonal antisera to synthetic peptides matching sequences on the cytoplasmic regions of connexin-43, a gap junction protein first identified in rat heart, have been used to immunolabel gap junctions in the calvarial bone, maintained intact as in vivo, of 1- to 2-week-old rats. The specimens were examined in reflection and fluorescence modes by scanning laser confocal microscopy, and the numbers of gap junctions and their sizes estimated. The mean number of connexin-43 immunolabelled junctions per osteoblast (n = 65) was 15.3 (SD +/- 4.5). The mean length of 227 junctions, selected for the sharpness of the image of the fluorescent spot, was 0.67 micron (SD +/- 0.18; range 0.37-1.29 microns) and their mean area 0.26 micron2 (SD +/- 0.145; range 0.075-0.93 micron2); these probably fell within the upper half of the total size range. Gap junctions were detected between preosteoblasts, osteoblasts, osteocytes and chondrocytes, and between these juxtaposed cell types. In addition, connexin-43 immunolabelled junctions were found between some osteoclasts and overlying mononuclear cells at active sites of resorption.
Development and use of a welding process exposure matrix in a historical prospective study of lung cancer risk in European welders.
A welding process exposure matrix has been developed relating 13 welding process-welded metal combinations to average exposure levels for total welding fumes, total chromium, chromium (VI) and nickel. Quantitative estimates were derived from consultation of literature sources and of some company data. This matrix was applied to the welding histories of 11,092 welders in the framework of an IARC multicentre study. When detailed welding history was not available at the individual level the average company welding practice profile was applied. No dose-response relationship emerged for lung cancer risk with cumulative dose of the carcinogens chromium (VI) and nickel for stainless steel welders. Dilution of the dose-response relationship could result from between-plant and within-plant variability, and exposure in jobs not accounted for in the study, but not from the partial use of company versus individual data. It is also possible that there is no increased risk related to chromium and nickel exposure in this group of workers. Matrix exposure estimates would need to be validated and the matrix possibly refined by comparison with a variety of comprehensive welding exposure data sets.
Personality and depression in Parkinson's disease.
The Parkinson's disease (PD) patient has been characterized as having a distinctive personality with introverted features. These personality traits are said to predate motor symptoms and are theorized to serve as a subtle clue to latent PD. To examine this hypothesis, we compared remote and current personality features in 35 PD subjects and 35 controls. Subjects' spouses completed a personality inventory (PI) characterizing patients' premorbid and current status. The premorbid PI of PD subjects differed from that of controls in being more "quiet," "generous," "cautious," and "even-tempered," and less "flexible." The characterization of the PD subjects' current personality differed greatly from reported premorbid personality features, i.e., significant change in 13 of 24 PI items. Personality inventory responses regarding both the PD subjects' premorbid and current personality correlated to symptoms of depression and disease severity. Cognition, tobacco use, alcohol consumption, and rural versus urban residency did not correlate with PI responses. We conclude that PD patients are apt to be viewed as introverts premorbidly, and, with disease onset, more striking personality changes are recognized. These perceptions appear to be closely linked to depressed affect and correlate with motor impairment to a lesser extent.
Fatal diltiazem overdose: report of four cases and review of the literature.
Four fatal cases of diltiazem overdose are described and compared with previously published cases. Clinical sequelae include all grades of heart block, hypotension and ultimately death. Management includes gastric lavage and oral administration of activated charcoal at presentation. Further symptomatic treatment with inotropic agents and temporary cardiac pacing may be required. If these measures are successful, recovery occurs within 36 hours in uncomplicated cases. Toxicological data have been reviewed but currently drug levels can only offer a retrospective analysis of the severity of overdoses. As the use and risk of abuse of diltiazem increases, these reports serve to highlight the possible hazards and to alert physicians to what must be regarded as a dangerous and potentially lethal drug in overdosage.
Identical twins with similar onset of Parkinson's disease: a case report.
The role of heredity in Parkinson's disease (PD) is controversial. We report a pair of monozygotic twins (confirmed by DNA fingerprints) concordant for PD. Their disease began when they were 62 and 63 years old. Both patients presented with left-side bradykinesia. One of the twins had a long history of depression. Both patients had typical manifestations of PD, which were responsive to dopaminergic therapy. The similar age of onset along with the similar clinical characteristics of these twins suggests that hereditary or genetic susceptibility may be important in the etiology of PD.