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Biomedical subjects

M Green

Publications and source records attributed to M Green.

At least 487 records · Page 27Linked to original sources
PubMed1989

Phase II trial of ICRF-187 in patients with acquired immune deficiency related Kaposi's sarcoma (AIDS-KS).

Thirteen patients with AIDS related Kaposi's Sarcoma were entered on a phase II trial of ICRF-187, 1000 mg/m2 IV daily for 3 days every 3 weeks. Eight patients had received prior chemotherapy for AIDS-KS. Six patients had prior opportunistic infection. There were no complete responses; one partial response lasting six months was seen. Toxicity was significant, and of the first 5 patients treated, 3 out of 5 had grade III or IV neutropenia. Because of this, subsequent patients received 800 mg/m2 IV days 1-3 if previously untreated or 600 mg/m2 if previously treated. Overall 4 of 13 patients had Grade IV neutropenia and 5 of 13 had Grade III neutropenia. One patient had Grade IV thrombocytopenia. ICRF-187 at a daily x 3 schedule has some efficacy in the treatment of AIDS related KS, future trials should evaluate lower doses or alternate schedules of administration.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Phase II study of carboplatin in recurrent ovarian cancer: severe hematologic toxicity in previously treated patients.

Carboplatin (CBDCA) is a second-generation cisplatin analog that has shown activity in early clinical trials. Its spectrum of toxicity is quantitatively and qualitatively different from that of the parent compound. Between November 1984 and September 1986 we conducted a phase II trial of CBDCA in 46 women with epithelial ovarian cancer. All patients had undergone at least one prior chemotherapy regimen; 41 (89%) had previously received cisplatin (mean cumulative dose, 540 mg/m2). The CBDCA dose was based on renal function and was injected i.v. once every 4 weeks. Patients were stratified on the basis of baseline creatinine clearance: those with a baseline creatinine clearance of greater than or equal to 60 ml/min received 400 mg/m2 CBDCA; those with a creatinine clearance between 30 and 60 ml/min received an initial dose calculated according to a previously published formula that corrected for renal insufficiency and projected nadir platelet counts of 75,000/mm3. Of 41 evaluable patients, 6 (15%) had an objective response [2 complete responses (CRs); 4 partial responses (PRs)]; 5 of the 6 responders had previously responded to cisplatin treatment. No responses were observed in 12 patients who had not responded to prior cisplatin therapy. Significant hematologic toxicity was seen. Of 18 patients with a creatinine clearance of greater than or equal to 60 ml/min (dose, 400 mg/m2), 6 had nadir platelet counts of less than 25,000/mm3, 4 with symptomatic bleeding. Of the 21 evaluable patients for whom the dose-modification formula was applied, 10 had nadir platelet counts of less than 75,000/mm3; 5 had counts of less than 50,000/mm3. CBDCA has activity even in patients who have previously undergone extensive cisplatin therapy; however, its toxicity is variable and thrombocytopenia is dose-limiting. We did not confirm the ability of the above-mentioned formula to calculate the CBDCA dose and accurately predict the nadir platelet count for all patients. Other factors, such as prior radiotherapy, may also be important in the dosing of CBDCA in pretreated patients.

Acute Disease↗
PubMed1989

Ambiguous-handedness: incidence in a non-clinical sample.

Using a handedness demonstration preference test under simple and complex task conditions, incidence rates for right, left, and mixed hand preferences were identified in a non-clinical sample. A relatively low incidence rate of ambiguous-handedness was also demonstrated, supporting earlier hypotheses that this subtype is rare among normals.

Adult↗
PubMed1989

A new system for port films.

A novel system for port films is described which incorporates a high-quality fluorescent screen lying behind a flat, heavy-metal screen or filter and the film pressed between them is not an X ray type but a single-emulsion, very high contrast graphics or line-type film. In experimental comparisons using 4 MV, 6 MV, and 25 MV photon beams, the new Peter MacCallum Cancer Institute (PMCI) system produced clearer images, about X2 higher in contrast yet lower in relative noise levels, than did the conventional commercially-available systems which use x-ray film between heavy-metal screens. Direct clinical comparisons, chiefly using 6 MV accelerators, confirmed that anatomical details were correspondingly better visualized and in general, the PMCI port film could be matched against the simulator radiograph with greater confidence. Routine use for greater than 2 yr in this Institute (4000 new patients per yr, 20 cassettes made for use with four 6 MV accelerators) has shown the PMCI system to be an economical and practical device, giving reproducibly high quality images in all the common port film applications.

Humans↗
PubMed1989

Ergonomic stress levels, personal characteristics, accident occurrence and sickness absence among factory workers.

This study was designed to evaluate the association of a single, integrated measure of simultaneous exposure to a number of adverse work and environmental conditions, termed the Ergonomic Stress Level (E-S-L), on workers' accident and sickness absence rates. The factors determining the E-S-L were body motion and posture, physical effort, active hazards and environmental stressors. E-S-L evaluation was based on 'walk-through' hazard inventories, direct observations, measurements and interviews. Workers were assigned to one of four stress levels ranging from low (A) to high (D). Subjects were 729 males, aged 20-67 years, employed in five factories in Israel. A linear relationship between E-S-L AND accident incidence was found, increasing from the lowest to the highest E-S-L. Moreover, workers more sensitive to environmental stressors, as indicated by their reported subjective annoyance, showed higher accident rates across all the ergonomic stress levels, a tendency which was statistically significant at levels C and D. On the other hand, sickness absence was significantly related to the overall subjective stress experienced, as manifested by reported job dissatisfaction and somatic complaints, and not directly to E-S-L. These findings highlight the role of aggregate work stress, coupled with individual sensitivity to environmental stressors, in increasing the risk of accidents.

Absenteeism↗
PubMed1989

A phase II study of carboplatin and CHIP in patients with metastatic colon carcinoma.

Fifty-six patients were treated in each arm of a study comparing CHIP and carboplatin for the therapy of previously untreated metastatic colorectal carcinoma. There were one partial response (2%) with CHIP and two partial responses (4%) with carboplatin. Side effects were significantly more severe with CHIP than with carboplatin. The most common side effect for both drugs was vomiting followed by hematologic side effects. Sixteen percent of the patients receiving CHIP and 9% of those receiving carboplatin had life-threatening side effects. Neither drug offers significant activity in metastatic colorectal carcinoma.

Aged↗
PubMed1989

Duration of hospitalization in previously well infants with respiratory syncytial virus infection.

To describe the typical hospital course of infection in previously well infants hospitalized with respiratory syncytial virus (RSV) infection, we reviewed the charts of 196 patients with laboratory-proved respiratory syncytial virus infection in the 1987-1988 respiratory disease season. Eighty-seven of the children had been previously well. Their mean duration of hospitalization was 3.4 days. Previously well infants younger than 6 weeks of age experienced significantly longer hospitalizations and more days of supplemental oxygen and were more likely to require intensive care than were older children. Children older than 12 weeks of age were hospitalized for a mean of 2.5 days and did not require intensive care. Oxygen saturation was measured in the emergency room for 67 of the previously well infants; in 42 oxygen saturation was at least 90% whereas in 25 saturation was less than 90% or infants were receiving supplemental oxygen at the time of measurement. Decreased initial oxygen saturation was associated with a prolonged hospitalization (5.3 vs. 3.2 days, P less than 0.01) and with more days of supplemental oxygen (4.4 vs. 1.5 days, P less than 0.01). We conclude that among previously well infants admitted to the hospital with respiratory syncytial virus infection, infants younger than 6 weeks of age are at increased risk for a prolonged and more severe hospital course than are older children.

Age Factors↗
PubMed1989

Why do amitriptyline and dothiepin appear to be so dangerous in overdose?

Data from different analyses of reported deaths from overdose with antidepressants in the U.K. reveal that amitriptyline and dothiepin are the antidepressants most likely to be associated with death from overdose. All widely used tricyclic antidepressants (TCAs) except clomipramine and lofepramine appear to be dangerous in overdose, whereas the newer antidepressants such as mianserin, trazodone, viloxazine and the TCA lofepramine appear to be relatively safe. The toxicity of amitriptyline and dothiepin appears to be greater than all antidepressants including other TCAs and it is important to try to understand why. A number of explanations will be considered: 1. Dothiepin and amitriptyline may be inherently more toxic than other TCAs. 2. Dothiepin and amitriptyline may induce suicide more than other antidepressants. It is assumed that antidepressants are neutral with regard to inducing suicide but this may not be true. There is, for example, evidence that alprazolam and other benzodiazepines induce suicidal behaviour. 3. Amitriptyline and dothiepin are often presented in subtherapeutic and ineffective doses and it is possible that increased suicides may result from inadequately treated depression. 4. There may be a selective overreporting of deaths with amitriptyline and dothiepin. 5. Amitriptyline and prothiaden may be selectively given to the suicide prone on the mistaken assumption that they are safe.

Amitriptyline↗
PubMed1989

Mutational analysis of bovine papillomavirus type 1 E5 peptide domains involved in induction of cellular DNA synthesis.

Early gene E5 of bovine papillomavirus type 1 encodes a 44-amino-acid protein whose expression can transform immortalized mouse cell lines. We have previously reported that a chemically synthesized E5 peptide functions to induce cellular DNA synthesis upon microinjection into growth-arrested mouse cells. We further defined the two E5 domains essential for the full DNA synthesis induction activity by the analysis of E5 deletion and amino acid substitution mutant peptides. The first domain is the C-terminal 13-amino-acid core which is sufficient to activate DNA synthesis at high peptide concentration and contains two essential, highly conserved cysteine residues. The second domain is the 7-amino-acid hydrophobic sequence contiguous to the core domain which is sufficient to confer a 1,000-fold higher molar specific activity to the E5 peptide. A random hydrophobic sequence, but not charged amino acids, fulfills the function of the second domain.

Amino Acid Sequence↗
PubMed1989

Mutational analysis of autonomously functioning trans-activating peptides encoded by adenovirus E1A: evidence for two subdomains.

We have shown previously that a chemically synthesized adenovirus E1A region 3 peptide of 49 amino acids, protein domain 3 (PD3; residues 140 to 188 of the 289-amino-acid protein), trans activates viral genes in vitro and in vivo. To study structure-function relationships, we synthesized N-terminal deletion and cysteine substitution mutant peptides and tested their activities in a cell microinjection assay. Peptides lacking 1 to 12 N-terminal residues exhibited 5- to 50-fold-reduced molar specific activities, whereas those lacking 16 or 18 residues were inactive. Substitution of each of five PD3 cysteine residues with alanine resulted in substantial losses of activity: mutants in the PD3 N-terminal portion showed 40 to 55% of wild-type activity but required a 20-fold-higher concentration than PD3, whereas those in the C-terminal half were as much less active. These peptide mutant studies suggest the existence of two PD3 functional regions: one, localized in the C-terminal 70 to 75% of the molecule, is essential for trans activation; the other, localized in the N-terminal 25 to 30%, can be overridden to a significant extent at high peptide concentrations.

Adenovirus Early Proteins↗
PubMed1989

'Dialysis related arthropathy': a survey of 95 patients receiving chronic haemodialysis with special reference to beta 2 microglobulin related amyloidosis.

Ninety five patients receiving chronic haemodialysis (CHD) were surveyed to determine the prevalence of rheumatic disease and, where possible, its aetiology. At least three distinct rheumatic syndromes were identified--a group of patients with a syndrome consisting of large and medium joint synovial swelling, restricted hips and shoulders, tenosynovitis, carpal tunnel syndrome, and bone cysts due to deposition of beta 2 microglobulin related amyloid (AM beta 2m); a second group with erosive azotaemic osteoarthropathy; and a third group with age related degenerative disease of small, large, and axial joints. The data presented suggest that in patients receiving CHD (a) the prevalence of AM beta 2m deposition and the associated syndrome increases with duration of dialysis, but in patients who have been dialysed for more than 10 years the risk of developing AM beta 2m is related to age; (b) AM beta 2m deposition in subchondral cysts, but not synovium, causes joint destruction; also, AM beta 2m may be more prone to deposition in synovium of joints already damaged by other processes; (c) in the absence of synovial iron deposition synovial AM beta 2m is not associated with an inflammatory infiltrate; (d) hyperparathyroidism and perhaps other factors such as synovial iron deposition are probably more important than AM beta 2m as causes of peripheral joint degeneration and destructive spondyloarthropathy in patients receiving CHD.

Adult↗
PubMed1989

Osteoporotic bone microstructure by collagenase etching.

Collagenase etching has been used to show the microstructure of bone from patients suffering from primary osteoporosis. Both polished and unpolished surfaces of trabecular bone from femoral heads were treated with collagenase solution before study in the scanning electron microscope. The polished surfaces show the mineral component of this bone as small rounded units approximately 10-20 nm across, which aggregate to form a continuous phase of contiguous spheroidal particles approximately 100 nm across. Lamellations are clearly seen to be due to the removal of collagen fibres up to approximately 200 nm across, fibres in adjacent lamellae being arranged approximately perpendicular to each other. The unpolished surfaces also show small rounded units, which aggregate into rods of mineral approximately 100 nm across. Although these rods form a connected system, they are loosely packed, compatible with their being interspersed with the collagen fibres in vivo. This model for the detailed microstructure of bone is consistent with specimens from a number of other sources and shows no features unique to osteoporosis.

Aged↗
PubMed1989

Respiratory muscle weakness in the Lambert-Eaton myasthenic syndrome.

Respiratory muscle function was assessed in six patients with the Lambert-Eaton myasthenic syndrome. Five had histologically proved small cell carcinoma of the lung; the sixth later developed metastases from an unknown primary site. Two patients had ventilatory failure, one without respiratory symptoms; another, who had emphysema, had dyspnoea and orthopnoea. The remaining three patients had no respiratory symptoms. Four patients had limb muscle weakness as judged by the maximal voluntary contraction of the quadriceps muscle (range for all subjects 32-100% predicted). Transdiaphragmatic pressure (Pdi) was measured during a maximal unoccluded sniff (Pdi: sniff), a maximal sustained inspiratory effort against a closed airway (Pdi: Pimax), and phrenic nerve stimulation (Pdi: twitch). Mild to moderate diaphragmatic weakness was present in all six patients in proportion to the degree of leg weakness (Pdi: sniff 30-64% predicted; r = 0.6; Pdi:Pimax 6-69% predicted, r = 0.8); this was associated with very low or absent Pdi:twitch during phrenic nerve stimulation. Four patients had weakness of the expiratory muscles. Improvement in muscle strength was documented in two patients after tumour chemotherapy and specific treatment with 3,4-diaminopyridine and prednisolone; one patient was still alive five years from first diagnosis. It is concluded that the respiratory muscles may be implicated in this condition more often than has previously been recognised. As the lack of mobility may cause respiratory symptoms to be minimised, the presence of respiratory muscle weakness may remain undiagnosed unless formal measurement of respiratory muscle function is made.

Autoimmune Diseases↗
PubMed1989

Twitch pressures in the assessment of diaphragm weakness.

To assess the value of phrenic nerve stimulation in the investigation of diaphragm function, transdiaphragmatic pressures were measured in 20 healthy subjects and in 15 patients with diaphragm weakness, during unilateral and bilateral transcutaneous phrenic nerve stimulation at 1 Hz at functional residual capacity (twitch Pdi). Diaphragm function was initially assessed by measuring transdiaphragmatic pressure during a voluntary manoeuvre, the maximal sniff (sniff Pdi); normal readings were confirmed in the control subjects (102-157 (normal greater than 98) cm H2O in the 10 men, 79-102 (normal greater than 70) cm H2O in the 10 women) and reduced values were found in the 15 patients with diaphragm weakness (7.5-90 cm H2O in the 13 men, 23 and 53 cm H2O in the two women). Twitch Pdi during bilateral phrenic nerve stimulation ranged from 8.8 to 33 cm H2O in the control subjects and from 3.1 to 27 cm H2O in the 10 patients in whom a measurement could be obtained. Bilateral twitch Pdi correlated with sniff Pdi both in the control subjects and in the patients with diaphragm weakness (r = 0.75). Only four patients had a bilateral twitch Pdi below the lowest value seen in the control group, including the three with the lowest sniff Pdi (3.1-8.5 cm H2O). These results indicate that transdiaphragmatic pressure recorded during bilateral phrenic nerve stimulation discriminated between control subjects and patients with known weakness of the diaphragm only when this was severe.

Adult↗
PubMed1989

Intermittent 3-day depressions and suicidal behaviour.

Intermittent short-lived episodes of depression were examined in a group of 20 recurrent suicidal attempters without major depression, classified misleadingly as borderline personality disorders on DSM-IIIR, during careful prospective follow-up for between 4 and 6 months. The duration of depressions clustered tightly around a median of 3 days with two thirds lasting between 2 and 4 days. They occurred erratically and unpredictably with a median interval of 18 days and were seen to be moderate to severe measured on the MADRS in 70% of episodes.

Crisis Intervention↗
PubMed1989

Prophylactic treatment of depression: a public health issue.

The majority of depressive illness is a chronic and relapsing, frequently occurring illness, which carries significant social and economic consequences for the sufferer. Depression is also associated with increased morbidity and mortality from physical illness and suicide. Long-term antidepressant treatment is needed for at least 6 months after the resolution of the symptoms of an acute episode to consolidate recovery. In recurrent depression, treatment over a much longer period is required to reduce the risk of a new episode occurring. It is clear from the prophylactic studies, which require careful and appropriate methods, that some half of the recurrent episodes of depression are preventable by adequate prophylactic treatment with antidepressants. This effect has been clearly demonstrated with some of the newly introduced 5-HT uptake inhibitors. The disadvantages of long-term treatment have to be weighed against the risks and costs, personal, social and economic, of the illness.

Antidepressive Agents↗