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Biomedical subjects

R Alexander

Publications and source records attributed to R Alexander.

At least 73 records · Page 4Linked to original sources
PubMed1996

Recognition of vitreoschisis in proliferative diabetic retinopathy. A useful landmark in vitrectomy for diabetic traction retinal detachment.

INTRODUCTION: In the late stages of proliferative diabetic retinopathy (PDR) the vascularized posterior cortical gel (PCG) contracts leading to a partial posterior hyaloidal separation, hemorrhage, and traction retinal detachment (TRD). "Additional epiretinal membranes" have been described previously. These are thin, usually transparent epiretinal membranes which extend anteriorly from the point of attachment of the elevated posterior cortical gel to the edge of the TRD. The origin and frequency of the occurrence as well as the clinical significance of such additional epiretinal membranes are the subjects of controversy. PURPOSE: To quantitate the authors' clinical impression that additional epiretinal membranes are common in advanced PDR, to characterize them immunohistochemically, and to demonstrate the rationale for the authors' surgical approach. METHODS: Intraoperative observations for all patients undergoing diabetic vitrectomy and delamination over the last 2 years were reviewed retrospectively. The presence of additional epiretinal membrane was searched for in the initial stages of vitrectomy. When identified, their apparent continuity with the elevated portion of the PCG was confirmed. Surgical specimens were obtained from nine patients for immunohistochemical study. RESULTS: Additional epiretinal membranes were observes in 145 (81%) of 179 consecutive eyes with PDR that underwent surgery for macular TRD. Immunohistochemical staining with type II collagen antibody was positive in all specimens, suggesting that these membranes were of vitreous origin. CONCLUSIONS: It is likely that the additional epiretinal membranes represent the posterior leaf of a split PCG, the anterior leaf being the elevated portion of the PCG. The two leaves remain fused in the main, fibrovascular portion of the epiretinal membrane. These findings help explain the clinical experience that once the posterior leaf of the PCG is identified and elevated, it provides an accurate point of entry into the surgical plane facilitating delamination of the fused (vascularized) portion of the PCG from the detached retina.

Aged↗
PubMed1996

The inhibition of antigen-induced eosinophilia and bronchoconstriction by CDP840, a novel stereo-selective inhibitor of phosphodiesterase type 4.

1. The novel tri-aryl ethane CDP840, is a potent and selective inhibitor of cyclic AMP phosphodiesterase type 4 (PDE 4) extracted from tissues or recombinant PDE 4 isoforms expressed in yeast (IC50S: 4-45 nM). CDP840 is stereo-selective since its S enantiomer (CT 1731) is 10-50 times less active against all forms of PDE 4 tested while both enantiomers are inactive (IC50S: > 100 microM) against PDE types 1, 2, 3 and 5. 2. Oral administration of CDP840 caused a dose-dependent reduction of interleukin-5 (IL-5)-induced pleural eosinophilia in rats (ED50 = 0.03 mg kg-1). The eosinophils in pleural exudates from CDP840-treated animals contained higher levels of eosinophil peroxidase (EPO) than cells from control animals, suggesting a stabilizing effect on eosinophil degranulation. CDP840 was approximately equi-active with the steroid dexamethasone in this model and was 10-100 times more potent than the known PDE 4-selective inhibitors rolipram and RP73401. The activity of CDP840 was not influenced by adrenalectomy, beta-sympathomimetics or beta-sympatholytics. 3. Antigen-induced pulmonary eosinophilia in sensitized guinea-pigs was reduced dose-dependently by CDP840 (0.01-1 mg kg-1, i.p.) and intracellular EPO levels were significantly higher. CDP840 was more potent in these activities than CT1731 or rolipram and comparable in potency to RP73401. 4. Rolipram or CDP840 were less active than dexamethasone in preventing neutrophil accumulation, or exudate formation in carrageenan-induced pleurisy in rats and thus do not exhibit general anti-inflammatory activity. 5. In sensitized guinea-pigs, aerosols of the antigen ovalbumin caused a dose-dependent bronchoconstriction demonstrated by an increase in pulmonary inflation pressure. Administration of CDP840 (0.001-1.0 mg kg-1, i.p.), 1 h before antigen challenge, resulted in dose-dependent reduction in response to antigen. This activity was not due to bronchodilatation since higher doses of CDP840 (3 mg kg-1) did not significantly change the bronchoconstrictor response to histamine. Rolipram was approximately 10 times less active than CDP840 in preventing antigen-induced bronchoconstriction. 6. These results confirm the observations that selective PDE 4 inhibitors reduce antigen-induced bronchoconstriction and pulmonary eosinophilic inflammation. CDP840 is more potent than rolipram in inhibiting native or recombinant PDE 4. Unlike the recently described potent PDE 4 inhibitor RP73401, CDP840 is more active than rolipram in the rat IL-5 model following oral administration. The novel series of tri-aryl ethanes, of which CDP840 is the lead compound, could be the basis of an orally active prophylactic treatment for human asthma.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

The pathology of cornea in Tangier disease (familial high density lipoprotein deficiency).

AIMS: To clarify the underlying causes of corneal opacification in Tangier disease. METHODS: Both corneas were removed at death from a 62 year old man with Tangier disease, and were examined by direct and transmission electron microscopy, histochemistry, biochemical analysis by thin-layer and gas-liquid chromatography after extraction, and by differential scanning calorimetry. RESULTS: Membranous inclusions in the stroma were seen on transmission electron microscopy. Direct analysis confirmed enrichment with phospholipids and cholesterol, with acyl patterns and proportions as ester broadly similar to those of normal cornea. Tangier cornea showed major thermotropic phase transitions in the range 28-37 degrees C, peak 30-33 degrees C, extending above profiles of normal clear cornea and without the complexity of those seen with cornea with heavy arcus involvement. CONCLUSIONS: Lipid accumulation underlies corneal opacification in Tangier disease. The excess material is mainly phospholipid and cholesterol esters. As at other sites which are below body core temperature, notably tonsil, accumulation may be enhanced by local impaired mobilisation of material as the phase transitions of the excess lipid present extend above ambient corneal temperatures.

Calorimetry, Differential Scanning↗
PubMed1996

The quality of life of persons with severe emotional disability: a review of empirical studies.

Following the deinstitutionalization of persons with serious mental illness from state hospitals, many persons with serious mental illness did not receive the care that they needed and encountered unexpected negative experiences. Among the negative experiences were frequent rehospitalizations, involvement in the criminal justice system, and homelessness. Seeing these negative outcomes, mental health professionals in the 1980s debated the quality of life of persons with severe and persistent mental illness and concluded that the main goal of treatment was to improve the quality of life of those afflicted. Thus, the quality of life became a critical variable in determining the effectiveness of mental health treatment. This paper reviews studies that used quality of life as an outcome measure in treatment services for persons with serious and persistent mental illness and the policy implications of these studies.

Affective Symptoms↗
PubMed1996

Mechanisms of facilitation in primed perceptual identification.

We investigated the mechanism that produces priming in perceptual identification. In Experiment 1, subjects studied a series of compound words (e.g., OUTDOOR, SIDELINE); in Experiment 2, subjects studied a series of pictures (photographs) of objects. All subjects later received perceptual identification tests in which old (primed) and new (unprimed) words (Experiment 1) or pictures (Experiment 2) were presented for varying durations and masked. In both experiments, performance for primed and unprimed stimuli was predicted essentially perfectly by a model that assumes that prior exposure to a stimulus results in increased visual information-acquisition rate when it is subsequently encountered. An ancillary purpose of Experiment 1 was to test whether or not priming occurs for recombined words (e.g., OUTLINE); there was no evidence for such priming at any exposure duration.

Adult↗
PubMed1996

Combination paclitaxel (1-hour) and carboplatin (AUC 7.5) in advanced non-small cell lung cancer: a phase II study by the Fox Chase Cancer Center Network.

We have previously reported a 62% response rate and 54% 1-year survival rate for patients with advanced non-small cell lung cancer (NSCLC) treated with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 24-hour infusion in combination with carboplatin, using area under the concentration-time curve dosing (FCCC 93-024). Myelosuppression proved dose limiting, but was substantially reduced by the routine use of granulocyte colony-stimulating factor during the second and subsequent cycles. Antitumor activity has been reported with minimal myelosuppression, with paclitaxel 135 and 200 mg/m2 given every 3 weeks by 1-hour infusion to patients with NSCLC. In November 1994, we initiated a phase II trial of paclitaxel 175 mg/m2 given over 1 hour, with carboplatin dosed to a fixed, targeted area under the concentration-time curve of 7.5 every 3 weeks. In the absence of grade 4 myelosuppression, paclitaxel was escalated on an intrapatient basis by 35 mg/m2 per cycle to a maximum dose of 280 mg/m2 by cycle 4. Granulocyte colony-stimulating factor was not routinely used. Eligibility stipulated advanced, measurable, chemotherapy-naive NSCLC. Of 47 patients accrued, 39 (83%) had Eastern Cooperative Oncology Group performance status 1. The median age was 64 years; 40 patients were evaluable for toxicity. Of the first 20 evaluable patients accrued (cohort A), myelosuppression was tolerable. Cumulative peripheral sensory neuropathy grade > or = 1 in 15 (75%) patients and grade 3 in six (30%), however, generally occurring at paclitaxel doses greater than 215 mg/m2, obligated removal from study of at least three patients, despite the absence of disease progression, and proved to be dose-limiting. Consequently, the protocol was revised: the starting dose of paclitaxel was reduced to 135 mg/m2, with intrapatient dose escalation of 40 mg/m2 per cycle to a maximum dose of 215 mg/m2, thus recapitulating the original dosing schema used in FCCC 93-024. To date, 25 patients have been enrolled in this second cohort (cohort B) and treatment has been better tolerated. Of 21 evaluable patients, 13 (62%) have experienced peripheral sensory neuropathy, but only one (5%) has been grade 3. Myelosuppression also has been less pronounced, with 33% grade 4 granulocytopenia and 13% grade > or = 3 thrombocytopenia in cohort B compared with 70% and 50%, respectively, in cohort A. Of the first 22 patients accrued to cohort A, 12 (55%) had major objective responses. Median event-free survival is 23 weeks and median survival is 47 weeks. Of 15 evaluable patients in cohort B, five (33%) have had major objective responses. It is too early to report survival data. In conclusion, paclitaxel by 1-hour infusion in combination with carboplatin at a fixed targeted area under the concentration-time curve of 7.5 is an active regimen in advanced NSCLC. Neurotoxicity, rather than myelosuppression, is dose and protocol limiting at paclitaxel doses exceeding 215 mg/m2.

Adult↗
PubMed1995

Far lateral disc herniations treated by microscopic fragment excision. Techniques and results.

STUDY DESIGN: This was a retrospective review of a consecutive series of patients who underwent excision of far lateral disc herniations by a paraspinal, muscle-splitting incision that spares the facet. OBJECTIVE: The authors describe the surgical technique in detail and review the results of surgical treatment. SUMMARY OF BACKGROUND DATA: As the lumbar nerve roots exit the intervertebral foramen, they once again lie in juxtaposition to an intervertebral disc and are susceptible to compression with subsequent radiculopathy. Radiculopathy caused by disc herniations in this area is less common, and the anatomy is less familiar to spinal surgeons than that of paramedian disc herniations. The involved root can be approached by a transfacetal approach or by a muscle-splitting approach that spares the facet. METHODS: Thirty-one consecutive patients had undergone the muscle-splitting approach to far-lateral disc herniations. Twenty-five (80.6%) of these patients were available for evaluation at a minimum of 2 years after surgery. Evaluation consisted of history, pain questionnaires, visual analogue scales, physical examination, and plain radiographs. RESULTS: Twelve patients (48%) had excellent results, eight (32%) had good, and five (20%) had either fair or poor results. Low back pain and dysesthesias were causes of unsatisfactory results. No radiographic sign of instability developed postoperatively. CONCLUSION: The anatomy of the nerve root lateral to the pedicle and our technique for microscopic excision of herniated disc fragments lateral to the facet are described. Our overall results were encouraging. The described microscopic technique will hopefully minimize dysesthetic pain that appears to be the result of the manipulation of the dorsal root ganglion.

Adult↗
PubMed1995

Comparison of different methods of administering droperidol in patient-controlled analgesia in the prevention of postoperative nausea and vomiting.

We performed a double-blind, placebo-controlled study to evaluate the different methods of administering droperidol in patients using patient-controlled analgesia (PCA) with morphine. Eighty patients undergoing major orthopedic procedures received temazepam 0.2 mg/kg orally followed by induction of general anesthesia with propofol 2.5 mg/kg, fentanyl 2 micrograms/kg, and vecuronium 0.1 mg/kg. Anesthesia was maintained with nitrous oxide, oxygen, and enflurane. At the end of surgery, all patients received PCA with morphine (0.5 mg/mL, bolus dose 1 mg, and lockout interval 5 min. Before commencement of PCA, patients were randomized to receive droperidol 1.25 mg immediately and, in addition, droperidol 0.16 mg with each PCA dose (Group 1), droperidol 1.25 mg immediately (Group 2), droperidol 0.16 mg with each PCA dose (Group 3), and no droperidol (Group 4). Incidence of nausea and vomiting, request for rescue antiemetics, sedation score, and side effects were recorded every 4 h. Droperidol significantly reduced the incidence of postoperative nausea and vomiting (PONV) (P < 0.01) and request for rescue antiemetic (P < 0.01) compared to placebo. However, there was no difference in the incidence of PONV between droperidol given either as a single dose at the end of surgery (Group 2) or mixed in morphine PCA (Group 3). The addition of droperidol in PCA after an initial dose (Group 1) should be avoided, as it resulted in more sedation and no further reduction in the incidence of PONV compared to Groups 2 and 3.

Adolescent↗
PubMed1995

Comparison of ondansetron and droperidol in reducing postoperative nausea and vomiting associated with patient-controlled analgesia.

In a randomised, placebo-controlled trial we have compared the efficacy of ondansetron and droperidol in reducing postoperative nausea and vomiting associated with patient-controlled analgesia after orthopaedic surgery. One hundred and forty five patients, ASA 1 and 2, undergoing major orthopaedic surgery were anaesthetised using a standardised technique. They were randomly allocated to receive patient-controlled analgesia as morphine 1 mg.ml-1 alone; morphine as before plus a single dose of 1.25 mg droperidol together with 0.083 mg.ml-1 in the infusion syringe; or morphine as before plus 4 mg ondansetron and 0.13 mg.ml-1 in the syringe. The patient-controlled analgesia bolus dose was set at 1 ml with a 5 min lockout and a 4 h maximum dose of 30 mg morphine. There was no background infusion. The occurrence of nausea, vomiting and sedation was assessed every 4 h. The incidence of vomiting decreased from 59% in the morphine-only group to 35% and 14% in the droperidol (p < 0.05) and ondansetron groups (p < 0.001) respectively. The number of patients suffering from nausea alone was not significantly different between the three groups, although those in the ondansetron group experienced less severe nausea (p < 0.05) when using a two point scale. The droperidol group had significantly higher sedation scores than the other two groups (p < 0.005). We conclude that ondansetron is superior to droperidol when used with patient-controlled analgesia and causes less sedation.

Adolescent↗
PubMed1995

Overuse injuries in classical ballet.

Successful management of classical ballet dancers with overuse injuries requires an understanding of the art form, precise knowledge of anatomy and awareness of certain conditions. Turnout is the single most fundamental physical attribute in classical ballet and 'forcing turnout' frequently contributes to overuse injuries. Common presenting conditions arising from the foot and ankle include problems at the first metatarsophalangeal joint, second metatarsal stress fractures, flexor hallucis longus tendinitis and anterior and posterior ankle impingement syndromes. Persistent shin pain in dancers is often due to chronic compartment syndrome, stress fracture of the posteromedial or anterior tibia. Knee pain can arise from patellofemoral syndrome, patellar tendon insertional pathologies, or a combination of both. Hip and back problems are also prevalent in dancers. To speed injury recovery of dancers, it is important for the sports medicine team to cooperate fully. This permits the dancer to benefit from accurate diagnosis, technique correction where necessary, the full range of manual therapies to joint and soft tissue, appropriate strengthening programmes and maintenance of dance fitness during any time out of class with Pilates-based exercises and nutrition advice. Most overuse ballet conditions respond well to a combination of conservative therapies. Those dancers that do require surgical management still depend heavily on ballet-specific rehabilitation for a complete recovery.

Ankle Injuries↗
PubMed1995

Home care challenges for those affected by AIDS.

AIDS is affecting more and more people, yet our health care system has been slow to respond to this growing population. Public interest has focused on AIDS as an acute illness while ignoring the chronically ill, homebound majority of persons with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Enhancing student practicum opportunities: the outbreak investigation option.

An outbreak investigation practicum option for graduate students at the University of Washington School of Public Health and Community Medicine has three goals of education, scientific investigation, and exposure to operations of public health agencies. Over a six-year period, 48 students performed 40 outbreak investigations in collaboration with adjunct faculty based in local public health agencies. An outbreak investigation practicum at Yale University had similar goals, but the rapid-response team approach there generally involved one regular faculty member and a team of graduate students. In either program, the level of faculty involvement necessary for outbreak investigations is sustainable only if the faculty value public health practice as part of the school's mission. Since public health students need to acquire many practical skills, a short outbreak investigation practicum experience should not be viewed in isolation, but rather should be one of a variety of practicum offerings available to students at schools of public health.

Curriculum↗
PubMed1995

Technetium-99m-sestamibi imaging before reoperation for primary hyperparathyroidism.

UNLABELLED: Recent studies have reported high sensitivities for parathyroid localization with 99mTc-sestamibi and have been performed using either 123I/99mTc-sestamibi or a double-phase sestamibi scanning technique. These studies have focused primarily on patients undergoing initial surgery. We studied 35 patients prior to reoperative surgery to investigate the relative sensitivities of these two technique sin this patient population. METHODS: Double-phase sestamibi scanning (early and delayed imaging) was performed in all patients. Evaluable 123I/99mTc-sestamibi subtraction studies were also obtained in 25 patients. Results were correlated with surgical findings in 32 patients and with clinical outcome in 3 patients in whom mediastinal lesions were radiographically ablated. RESULTS: Overall, double-phase sestamibi imaging detected 23 of 39 abnormal parathyroid glands (59%), whereas 123I/99mTc-sestamibi detected 19 of 27 (70%). Oblique imaging, delayed imaging and 123I subtraction all contributed to sensitivity, and 123I subtraction also proved useful in patients with partial thyroid suppression. Two patients had lesions visible on the early sestamibi images that were not seen at all on the delayed scans. There were four false-positive findings. CONCLUSION: No significant differences between double-phase sestamibi and 123I/99mTc-sestamibi subtraction scanning were found, although the latter tended to be more sensitive.

Adenoma↗