In search of the machinery for spatial patterning of animal epithelia.
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Biomedical subjects
Publications and source records attributed to R Phillips.
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Retinal exudates are a common manifestation of vascular damage in a variety of retinal diseases. We have used computerized image analysis to detect and measure the area of exudates from digitized colour fundus slides of patients with diabetic retinopathy and have assessed the repeatability, reproducibility, and accuracy of the technique. The analysis was entirely independent of the operator apart from choice of the region to be analysed. The coefficient of variation for repeatability was between 3% for large areas of exudate and 17% for small areas of exudate. The reproducibility was also within this range. Sensitivity was between 61 and 100% (mean 87%). False-positives were observed in 5 of 30 regions analysed, and these could have been eliminated by using more stringent criteria for selection of images for analysis. Time taken for the analysis was approximately 3 min.
OBJECTIVE: To compare the cardiac safety and therapeutic efficacy of trimipramine and doxepin. DESIGN: A 1-week single-blind placebo period followed by a 5-week randomized double-blind parallel group clinical trial. SETTING: Psychiatric out-patient clinic of a general hospital. PATIENTS: 37 young-elderly patients with a diagnosis of Major Depressive Episode (DSM-III criteria). INTERVENTIONS: Placebo for 1 week, 2 weeks of titration with either drug in the dosage range of 75 mg/day up to a maximum of 200 mg/day. MEASUREMENTS: We measured the psychiatric effects with the Hamilton Rating Scale for Depression, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression Scale. Cardiovascular effects were assessed on 12-lead standard electrocardiograms plus 1-minute rhythm and high speed recordings; orthostatic (lying/standing) blood pressures were also taken. Physical exams, lab tests, cognitive functions (Buschke Selective Reminding Test, Hierarchic Dementia Scale, Word Fluency) and adverse reactions were also noted. RESULTS: Both drugs were equally effective in relieving symptoms of depression and anxiety. The cardiovascular effects of both drugs were minimal. Trimipramine did lower blood pressure but this was without clinical significance. Three trimipramine patients and five doxepin patients developed occasional premature ventricular or atrial contractions. Of these, two trimipramine patients and one doxepin patient were among those with abnormal ECG's at entry. The doxepin patient was withdrawn from the study after 21 days of treatment when the PVC's became increasingly frequent. CONCLUSIONS: Trimipramine and doxepin are equally safe and effective antidepressants in the young-elderly.
We performed a single blind controlled multicenter study in which we compared the efficacy and safety of 100 mg of doxycycline versus those of 1 g (3 x 10(6) IU) of spiramycin given orally twice daily for 14 days in the treatment of culture-positive Chlamydia trachomatis genitourinary tract infections. A total of 367 patients were enrolled in the study, and 364 patients were evaluable for safety and 265 patients were evaluable for efficacy. The cure rate between treatment groups was not statistically significant, being 98% (125 of 128 patients) in the spiramycin group and 100% (133 of 133 patients) in the doxycycline group. Female patients who received spiramycin were more likely to report dysethesias that resolved after the completion of therapy. The results of the study show that spiramycin is an effective drug for the treatment of C. trachomatis infection and warrants further assessment over a shorter treatment period (7 days) and during pregnancy.
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Investigation of fetal nephrotoxicity by maternally administered nephrotoxins is hampered by many constraints, including the maternal effects of the nephrotoxin, the ability of the nephrotoxin to cross the placenta and the difficulties associated with direct fetal intervention. In the pouch young of the North American opossum, Didelphis virginiana, we describe the toxic effects of a heavy metal on the immature metanephric kidneys. Varying doses of uranyl nitrate, a heavy metal salt, were administered to opossum pups in the pouch approximately 20 days after birth and the kidneys were harvested 3 to 12 days later for histological analysis. Group 1 consisted of 4 untreated and 5 saline treated pups. Group 2 (9 pups) received 10 to 15 mg./kg. intraperitoneal uranyl nitrate. Group 3 (6 pups) were given a uranyl nitrate dose of 25 mg./kg. Group 4, the high dose group, received either 58 mg./kg. (3 pups) or 87 mg./kg. (3 pups) of intraperitoneal uranyl nitrate. Group 1 kidneys demonstrated no pathological changes except for some mild renal tubular vacuolization seen in the saline treated animals. In group 2 tubular dilatation and necrosis were present 3 days after treatment; tubular regeneration could be seen by day 7. In group 3 glomerular cystic changes, interstitial fibrosis and tubular regeneration were present by day 7. Some restoration of normal architecture occurred by day 12 with fibrosis apparent. Group 4 animals demonstrated much more pronounced cystic changes of glomeruli and tubules as early as day 5 with marked interstitial fibrosis and prominent tubular regeneration. By day 12 group 4 pups continued to demonstrate significant and severe glomerular and tubular cystic changes with marked interstitial fibrosis. Inflammation, although present in all groups (except control), was never prominent. This first description of the effect of heavy metal toxicity on the immature metanephric kidney could provide an insight into the mechanisms of disordered kidney growth.
The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the blood pressure and renal function of essential hypertensive patients depend on the specific type of NSAID and antihypertensive drug administered. Twelve patients with essential hypertension, aged 35 to 59 years, stabilized (blood pressure less than 140/90 mmHg) with captopril, received ketoprofen (100 mg bid for 7 days) or matching placebo in a randomized double-blind cross-over fashion. A 3-week wash-out period was included between treatment periods. Blood pressure on the first and last days of the placebo treatment period (137 +/- 7 (SD)/80 +/- 8 and 139 +/- 11/81 +/- 9 mmHg) was similar to respective values during ketoprofen therapy (136 +/- 10/79 +/- 7 and 143 +/- 10/81 +/- 9 mmHg). The mean differences in systolic and diastolic blood pressures, at the end of the treatment periods, between ketoprofen and placebo were 4 (95% confidence intervals -5, +13) and 0 (-8, +8) mmHg, respectively. Ketoprofen had no effect on 24-h urinary sodium excretion (160 +/- 33 and 147 +/- 39 mmol/24 h for ketoprofen and placebo, respectively). Ketoprofen was without effect on glomerular filtration rate, renal plasma flow and filtration fraction. In conclusion, our data suggest that ketoprofen is a safe choice when short-term treatment with a NSAID is indicated in an essential hypertensive patient treated with a converting enzyme inhibitor such as captopril.
Forty-five previously untreated patients with primary carcinoma of the vagina were treated with curative radiotherapy from 1965 through 1985. All patients were staged according to the FIGO system. One patient was classified as Stage 0, 15 as Stage I, 22 as Stage II, 6 as Stage III, and 1 as Stage IV. Treatment consisted of intracavitary irradiation alone in Stage 0 patients. Stage I patients received intracavitary/interstitial irradiation alone or in combination with external irradiation and an implant when feasible. When treated with an implant only, the total tumor dose delivered was between 65-70 Gy. External irradiation consisted of delivering a dose of 45-50 Gy over a period of 4 1/2-5 weeks to the whole pelvis to treat the regional lymph nodes. An additional dose of 20-25 Gy was delivered to the site of original involvement using an implant when feasible. If not technically feasible, as in advanced stages, the patient was treated with additional external irradiation to a total dose of 65-70 Gy by a shrinking field technique. All patients except one were followed either until death or for a minimum of 2 years. The actuarial 5-year survival rates were 100% for Stage 0, 78% for Stage I, and 71% for Stage II patients. None of the patients with Stage III or IV disease survived. Of the patients who recurred, all but two did so within 16 months after diagnosis. Pelvic recurrence as the first site of recurrence occurred in 86% of the patients who recurred. Distant recurrence as a component occurred in 20% of all failures. Complications as a consequence of therapy occurred in 18% of the patients. Vaginal necrosis that healed with conservative treatment was seen in four patients and the other four patients had rectal complications of varying severity. Thus, curative radiotherapy is an effective method of treatment, with acceptable morbidity, in patients with early stage primary carcinoma of the vagina.
The epidemiologic features and clinical spectrum of pertussis in the elderly are poorly understood. In October 1985, the Wisconsin Division of Health investigated an outbreak of pertussis in residents of a nursing home in rural Wisconsin. Clinical information and nasopharyngeal swab and acute- and convalescent-phase serum specimens were obtained from all consenting residents and employees. Of 105 residents, 38 (36.2%) were seropositive, including four who were culture-positive for Bordetella pertussis. Culture-positive residents (age range, 52-81 years) had cough lasting 43-54 days. Three of these residents had paroxysmal cough, and all four had cough that interrupted sleep; none of the residents had cough with apnea or vomiting, and all recovered without sequelae. Of six seropositive residents with clinical pertussis, five lived on the south wing of the facility. Of 104 employees, 8 (7.7%) were seropositive, but none were culture-positive for B. pertussis. The higher attack rate for residents and the clustering of clinical cases were consistent with ongoing transmission within the nursing home.
The postantibiotic effect (PAE) of fluoroquinolones against Staphylococcus aureus was determined in Mueller-Hinton broth and normal human serum. At both 4X and 10X the MIC, serum significantly increased the duration of the PAE in all strains tested (P less than 0.05). Reducing the pH of the serum from 7.9 to 7.2 had no effect on the PAE. Heat treating the serum (56 degrees C, 30 min) reduced the PAE of ciprofloxacin at 10X the MIC approximately 25% (P less than 0.05). The PAE of cloxacillin was reduced approximately 80% in serum, and PAE experiments with gentamicin and cephalexin produced findings similar to those obtained with the fluoroquinolones. Serum increased the MICs of ciprofloxacin and norfloxacin less than twofold and increased the MIC of pefloxacin approximately fourfold. We conclude that normal human serum considerably increases the PAE of fluoroquinolones against S. aureus.
Most patients with moderate to severe head injury initially do not tolerate enteral feedings postinjury. This intolerance is more prolonged than that found in patients suffering other types of trauma. The authors prospectively evaluated 12 patients with moderate to severe head injury (Glasgow Coma Scale score between 4 and 10) throughout their hospitalization for liquid gastric emptying as a possible mechanism for intolerance to enteral feeding. During Week 1, the majority of patients displayed a delay in gastric emptying. Patients also displayed an abnormal biphasic response (gastric emptying faster than normal during the early stage but prolonged later). By Week 2, many patients still had delayed and abnormal biphasic responses to gastric emptying. By Week 3, an improvement was observed with the majority of patients exhibiting rapid gastric emptying, but delays and abnormal biphasic responses were still seen. Patients who initially had rapid or normal gastric emptying tolerated full-strength full-rate feedings significantly earlier compared with those who experienced delayed gastric emptying (8.5 +/- 0.5 days vs. 13.7 +/- 3.2 days, p less than 0.001). All patients tolerated full-strength full-rate feedings by Day 16 postinjury (range 7 to 16 days) except the two patients who displayed delayed gastric emptying for prolonged periods of time (mean 25 days). This is the first study to longitudinally evaluate gastric emptying following head injury. The authors suggest that patients with moderate to severe head injury often experience alterations in gastric emptying which may affect their ability to tolerate enteral feedings.
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Patients with severe head injury have a disruption in metabolic homeostasis that includes increased energy expenditure and increased protein catabolism. These changes have been suggested to occur secondary to steroid administration, immobility, and other factors. A review of investigations indicates that the head injury itself causes these metabolic changes, although steroid administration can further alter plasma amino acid changes. Altered plasma amino acid profiles after head injury may have an effect on substrate availability to the brain, bacterial translocation, and overall nitrogen balance. Patients with severe head injury have increased skeletal muscle efflux of amino acids. Lack of nutrient supplementation in these patients is associated with increased morbidity and mortality. Enteral nutrition is the preferred mode of feeding but often is not tolerated in the patient with head injury. Parenteral nutritional support can be given to these patients without worsening cerebral edema.
The cytokine interleukin-6 (IL-6) plays a major role in initiating the acute phase response, especially in the production of acute phase reactants such as C-reactive protein. The objectives of this study were to determine whether plasma or ventricular fluid IL-6 levels were elevated at time of admission after head injury and whether plasma IL-6 levels related temporally to clinical improvement of levels of acute phase reactants. Thirty patients with Glasgow Coma Scale (GCS) scores of 3 through 10 were observed for 15 days after head injury. Peak elevation of plasma IL-6 occurred on admission (85 +/- 12 U/ml; normal level is less than 2 U/ml) and then decreased during the hospital course to a level of 29 +/- 4 U/ml on day 15. Plasma IL-6 levels decreased significantly faster in patients with admission peak 24-hour GCS scores of 8 through 10 compared with patients with GCS score less than 8 (p less than 0.01). Patients had markedly elevated and variable ventricular fluid IL-6 levels on admission (mean 3880 +/- 2022 U/ml; normal, less than 2 U/ml). A temporal relationship was found between plasma IL-6 levels and multiple acute phase reactants thought to be mediated by IL-6. We conclude that plasma and ventricular fluid levels of IL-6 are elevated after head injury and that plasma IL-6 level is temporally related to acute phase reactants and clinical improvement. We suggest that IL-6 may play an etiologic role in many of the metabolic or nutritional sequelae of head injury.
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Epidural gas occurring in benign disease is well documented. Gas formation within an epidural metastasis, which has not been previously reported, was demonstrated using computed myelography.
A total of 162 patients (134 males and 28 females) scheduled for coronary artery bypass grafting (144) or valve surgery (18) were randomly assigned to receive, under double-blind conditions, either pefloxacin 400 mg iv or cefazolin 1.0 g 30 min before the surgical incision and then post-operatively 12-hourly x 4 or 6-hourly x 8, respectively. Positive per- and post-operative cultures were seen in 27 patients (11 pefloxacin, 16 cefazolin) and 47 micro-organisms were isolated: 34 per-operatively (21 pefloxacin, 13 cefazolin) and 13 post-operatively (4 pefloxacin, 9 cefazolin). There were five failures of prophylaxis (2 pefloxacin, 3 cefazolin): two early (less than 5 days: 1 pefloxacin, 1 cefazolin) and three late (greater than or equal to 5 days, 1 pefloxacin, 2 cefazolin) divided into (i) one major primary failure in the cefazolin group (1 cefazolin resistant Staphylococcus epidermidis mediastinitis); (ii) two minor primary failures, one in each group (Gram-positive sternal incision abscesses) and (iii) two secondary failures (1 cefazolin resistant Enterobacter cloacae and Pseudomonas aeruginosa UTI in the cefazolin group and one culture negative pneumonia in the pefloxacin group). Tolerance to both antibiotics was excellent. In our sample of patients, the efficacy and safety of pefloxacin was not different from those of cefazolin in prophylaxis in cardiovascular surgery.