Biomedical subjects
M Ridley
Publications and source records attributed to M Ridley.
Postoperative accelerated radiotherapy in high-risk squamous cell carcinoma of the head and neck: long-term results of a prospective trial.
BACKGROUND: For patients treated with combination resection and postoperative radiotherapy, the interval between surgery and completion of radiotherapy represents an opportunity for tumor repopulation and treatment failure. A prospective trial to test the feasibility and efficacy of accelerated postoperative radiotherapy was concluded in August of 1990. METHODS: Thirty-two patients with high-risk pathologic findings were treated with 63 Gy in 35 fractions of 1.8 Gy over 5.2 weeks using a modified concomitant-boost technique. RESULTS: Acute mucosal and skin reactions were increased but tolerable. At a median follow-up of 6 years, the crude in-field recurrence rate for the entire group was 10/32 (31%), with 0/10 (0%) recurrences in patients commencing accelerated radiotherapy within 4 weeks of surgery and 10/22 (45%) recurrences in patients with a delay of more than 4 weeks (p = .006). The rate of late complications appears similar to that seen with conventional radiotherapy, with possibly a higher rate of "consequential"-type late effects. CONCLUSIONS: This pilot study suggests that prompt application of accelerated postoperative radiotherapy significantly improves local-regional control and supports the concept of rapid tumor repopulation in the postoperative setting. Various strategies to overcome tumor repopulation are discussed.
Non-independence in statistical tests for discrete cross-species data.
The paper described three previously undetected effects, due to biases and non-independence, that can arise in statistical tests for associations between character states in cross-species data. One kind, which we call the family problem, is general to all known methods. In phytogenetic data, the ancestral character state from which changes occur, or below which variation is found, is likely to be the same for many regions of the tree. The family problem interacts with two kinds of non-independence that arise because of the methods of reconstruction of character states that existing tests use. Different kinds of non-independence arise in methods that reconstruct joint, or single, character states, respectively. Methods, like Ridley's (1983), that work with joint character states suffer from the problem that a character state cannot change to itself with parsimony. Other methods that work with single character states suffer from the problem that within a locally variable region of the tree it is more likely with null data that there will be two single changes in the two characters in separate branches than one double change in both; associations opposite to the locally ancestral state are therefore likely to be found in more than 50% of the variable regions. In real data sets, the family problem acts to spotlight the other kinds of bias: if the family problem is large the bias in tests due to the way they reconstruct characters will be large, whereas if it is small, the local biases tend to cancel and disappear in the aggregate.
A new model for discrete character evolution.
The paper provides an explicit justification for the principle that a uniform taxon should contribute only one datapoint in comparative analyses with discrete variables. The justification is that phylogenetic patterns in variables unincluded in the proposed test vitiate the assumption of independence, both at the level of species and at the level of branch segments. The consequence is that a uniform taxon cannot safely be counted as more than one datapoint. The arguments use a branching discrete Markov process in continuous time, with the new feature that the tested variables are only a subset of the evolving characters. This model is proposed as a useful criterion for measuring the merit of proposed tests, and illustrates the necessity for models in evaluating comparative methods.
Brief communication: pelvic sexual dimorphism and relative neonatal brain size really are related.
Primate species in which the neonatal brain size is large relative to the birth canal tend to have more sexually dimorphic pelves: this is a classic comparative relation, discovered by Schultz and Leutenegger. The original work did not correct for phylogenetic nonindependence of the data points; it only partly corrected for body size; it used ratios in both variables, and the size of the female pubis featured in both x- and y-variables. A recent publication by Tague placed a question mark over the validity of the relation. I therefore retested it, correcting for all four statistical defects. A strongly significant statistical relation exists.
Comparison of intravenous ketorolac and alfentanil as supplements to propofol anesthesia for diagnostic panendoscopy.
STUDY OBJECTIVE: To determine if ketorolac tromethamine is an acceptable alternative to alfentanil as a supplement to propofol for diagnostic panendoscopy. DESIGN: Randomized, double-blind study. SETTING: University medical center. PATIENTS: 40 patients scheduled for panendoscopy and laryngeal tissue biopsy. INTERVENTIONS: Patients were randomly assigned to receive either alfentanil 14.5 micrograms/kg or ketorolac 1.0 mg/kg in a double-blind fashion, 5 to 10 minutes before induction of general anesthesia. MEASUREMENTS AND MAIN RESULTS: Heart rate (HR) and noninvasive blood pressure (BP) were measured and recorded before and immediately after injection of the study drug, after laryngoscopy for the endotracheal tube placement, and after initiation of diagnostic panendoscopy. Bleeding in the operative field was rated by the endoscopist. Observation from discontinuation of the propofol infusion and nitrous oxide inhalation to eye opening, head lifting, and orientation to time and place was observed and recorded. The presence of stridor after extubation, and pulse oximeter-determined arterial blood oxyhemoglobin saturation immediately after extubation and 5 minutes later, were noted. In the recovery room, the ability to tolerate oral fluids, sit, stand, and walk were recorded. Supplementation with ketorolac provides faster recovery from anesthesia as evidenced by shorter time to eye opening, head lifting, and orientation to time and place. However, no intergroup differences were found in measured intraoperative variables (BP and HR following laryngoscopy, tracheal intubation, diagnostic panendoscopy, and tissue biopsy). Operative site bleeding was comparable in both groups. The variables reflecting street readiness and the incidence of nausea and vomiting were statistically comparable. CONCLUSION: Supplementation of propofol anesthesia with ketorolac is an efficacious alternative to supplementation with alfentanil. The faster recovery in the ketorolac group is explained by the mostly peripheral effect of this drug, whereas the slow decline in the alfentanil concentration at the effective site may be responsible for slower emergence from anesthesia.
Altered p53 expression and epidermal cell proliferation is seen in vulval lichen sclerosus.
Aberrant p53 immunoreactivity has been found in skin pre-malignancies and dysplasias such as Bowen's disease and actinic keratoses. Vulval lichen sclerosus (LS) has been reported to be pre-malignant, with an association of vulval carcinoma in 3% to 6% of patients. In contrast, non-genital LS appears to have no malignant potential. In this immunocytochemical study, we investigated p53 expression in 10 cases of histologically proven vulval LS and 9 cases of non-genital LS using the murine monoclonal antibody Do-1 raised against recombinant human p53 which reacts with both wild-type and mutant p53. None of the vulval specimens had epithelial dysplasia or malignancy. Normal vulval (7 cases) and non-genital skin (5 cases) were used as tissue controls, respectively. The cell proliferation index was also studied using the MIB 1 monoclonal antibody which detects the cell-cycle associated Ki-67 antigen. The technique of microwave irradiation for antigen unmasking was employed on formalin-fixed and paraffin-embedded tissues. There was a significant increase in p53 immunoreactivity in vulval LS (32.13 +/- 15.11 epidermal cells per 100 basal cells) compared to normal vulval skin (7.52 +/- 5.04 epidermal cells per 100 basal cells) (p < 0.001), whereas the MIB 1 labelling index was lower in vulval LS (39.45 +/- 15.88 epidermal cells per 100 basal cells) than in normal controls (86.26 +/- 32.31 epidermal cells per 100 basal cells) (0.001 < p < 0.01). In contrast, there was no significant difference in p53 immunoreactivity or MIB 1 labelling index between non-genital LS and normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)
A prospective trial of accelerated radiotherapy in the postoperative treatment of high-risk squamous cell carcinoma of the head and neck.
PURPOSE: To evaluate the feasibility and toxicity of accelerated fractionation in the postoperative setting in high risk squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: Thirty-two patients with high risk pathologic features (e.g., extracapsular extension, positive margins, > or = 4 nodes positive, perineural invasion) were enrolled in an accelerated fractionation schedule, using a modification of the M.D. Anderson concomitant boost technique delivering 63 Gy in 5.3 weeks at 1.8 Gy per fraction. RESULTS: Thirty patients (94%) completed treatment per protocol. Confluent mucositis was seen in 22 (69%) and five patients (22%) required 2 to 4 months for complete healing. Only five patients (16%) lost more than 10% of body weight. At a median follow-up of 32 months (range 22-42 months), the crude infield failure rate is 8/32 (25%). Infield recurrence was significantly associated with the interval from surgery to commencement of radiotherapy; 0/10 (0%) patients beginning radiotherapy within 4 weeks of surgery had infield failures compared to 8/22 (36%) for patients beginning radiotherapy more than 4 weeks after surgery (p = 0.035). CONCLUSION: While acute side effects appear to be increased compared to conventional radiotherapy, we conclude that postoperative accelerated radiotherapy is feasible and has acceptable toxicity in this population. These results support the concept of rapid tumor repopulation after resection. A randomized multi-institutional trial is currently underway to compare conventional and accelerated fractionation in the postoperative setting.
Swallows and scorpionflies find symmetry is beautiful.
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Mandible reconstruction with vascularized bone grafts. A histologic evaluation.
To our knowledge, a histologic evaluation of bone healing after mandible reconstruction with vascularized human bone grafts has not been previously reported. Serial sections through both the decalcified graft and the junction between mandible and graft were evaluated in four patients who required surgical removal of their reconstructed mandibles. A failed scapular bone graft that had been wrapped within a pectoralis major myocutaneous flap for salvage following pedicle thrombosis showed markedly resorbed but viable bone with a fibrous union to the native mandible. Viable vascularized grafts without evidence of ongoing resorption characterized an iliac osteocutaneous bone graft and two scapula osteocutaneous grafts that healed with continuity of healthy bone between graft and mandible. Observations from the evaluation of these specimens are made regarding bone circulation, bone union, and bone graft survival as they occur clinically. Implications regarding the techniques of bone plating and indications for use of vascularized bone in mandible reconstruction are discussed.
Comment on the articles by Firestein and Zvaifler.
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Heart disease: a contemporary issue.
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Retinal angiomatosis: the ocular manifestations of von Hippel-Lindau disease.
The ocular manifestations of a large von Hippel-Lindau pedigree are presented. Of 24 persons with retinal angiomas, 18 are living and are the basis of this report. Nineteen of their 28 affected eyes were asymptomatic with 2 to 4 small tumours per eye. Nine eyes had lost vision secondary to exudative detachment. Seven of these had peripheral disease with rapid recurrences. Two had untreated disc tumours. Tumours less than 1 disc diameter (DD) in size were easily treated with photocoagulation. Multiple treatments of cryotherapy were required for larger tumours. Scleral buckle and early vitrectomy are recommended for vitreous traction. Tumour in a 4-year-old and a de-novo tumour in a 42-year-old lead us to recommend life-time surveillance of patients at risk. Many patients had false negative family histories. A review of the literature leads us to suspect that the majority of retinal angiomas are familial. We emphasize the ophthalmologist's responsibility to investigate such patients.
Private...public relationships.
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Lipemic diabetic retinopathy.
A study group of eight patients with diabetic retinopathy and marked accumulation of hard exudates in the fundi is described. There was a significant increase in serum triglyceride levels (P less than 0.05) in the study group as compared to a control group of 23 consecutive patients with diabetic retinopathy. This exudative disorder is visually disabling and is associated with legal blindness in 50% of eyes. The authors believe that the term most appropriate to describe such a severe type of exudative response is lipemic diabetic retinopathy.
Are organisms gene machines?
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Retinal pigment epithelial tears.
Retinal pigment epithelial tears have been recognized recently as a complication of retinal pigment epithelial detachments. They are characterized by sudden separation of detached from attached pigment epithelium at the margin of the detachment. Retraction of the overlying pigment epithelium occurs and exposes Bruch's membrane and choroid. Most pigment epithelial tears appear to arise spontaneously, but they also may occur following krypton red laser photocoagulation. The visual prognosis is poor in eyes in which the tear involves the subfoveolar pigment epithelium.