Variegate (mixed) porphyria in a Nigerian girl.

A fatal case of variegate (mixed) porphyria in an 11-year-old Nigerian girl is reported. She presented with severe abdominal pain, vomiting, constipation, quadriplegia and cutaneous bullous dermatosis. Remission was temporarily achieved with chlorpromazine, high carbohydrate diet and physiotherapy. She finally died of respiratory paralysis 17 months after diagnosis.     

Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators

BACKGROUND: The long acting beta 2 agonist formoterol has proved to be an effective bronchodilator with a prolonged action of 12-14 hours. However, the precise role of formoterol in the maintenance treatment of asthma is still under debate. A study was performed to investigate the efficacy and safety of treatment with formoterol for six months in subjects with asthma. METHODS: In a multicentre double blind, placebo controlled, parallel group study 239 subjects with mild to moderate asthma were randomly assigned to treatment with either inhaled formoterol 24 micrograms twice daily (n = 125) or placebo (n = 114) during eight months. The study consisted of a four week run in period, a 24 week treatment period, and a four week washout period. All subjects were using regular inhaled corticosteroids (100-3200 micrograms daily) but were still needing at least five inhalations of short acting beta 2 agonist per week for symptom relief. The study was performed in 10 outpatient clinics in Canada, and five outpatient clinics and one coordinating centre for 44 Dutch general practitioners in The Netherlands. Twice daily self-reported peak expiratory flow (PEF) measurements, symptom scores, and rescue beta 2 agonist use during the last 28 treatment days compared with baseline values were used as main outcome measures. Spirometric values were measured at entry, at the start of treatment, after four, 12 and 24 weeks of treatment, and after four weeks washout. RESULTS: One hundred and twenty five subjects received formoterol 24 micrograms twice daily via Turbohaler and 114 received placebo. Baseline FEV1 was 67.1% predicted and mean bronchodilator reversibility was 26%. The mean total asthma symptom score was 3.6 (maximum possible 21). A significant decrease in symptoms in favour of formoterol (difference from placebo -0.64, 95% CI -0.04 to -1.23, p = 0.04) was observed. Compared with placebo, morning PEF increased (difference from placebo 28 l/min, 95% CI 18.3 to 37.7, p = 0.0001) and the use of short acting beta 1 agonists decreased (daytime difference from placebo -1.1 inhalation, 95% CI -1.4 to -0.7, p = 0.0001) in the formoterol group. PEF returned to baseline following discontinuation of formoterol, as did asthma symptom scores. Thirty three patients treated with formoterol and 32 treated with placebo required treatment with prednisolone during the study (58 and 55 courses, respectively). CONCLUSIONS: Adding formoterol 24 micrograms twice daily by Turbohaler to inhaled corticosteroids was effective in improving symptom scores and morning PEF, and decreasing the use of rescue beta 2 agonists. There was no apparent loss of asthma control during 24 weeks of treatment with formoterol.


     

Sequential Adjuvant CMF Chemotherapy Followed by Radiotherapy in the Treatment of Early-Stage Breast Cancer: The Lankenau Hospital Experience

Abstract: The optimal timing of systemic cyclophosphamide, methotrexate, 5-fluorouracil (CMF) chemotherapy and local radiation in adjuvant breast cancer has been a debatable subject. To evaluate the Lankenau Hospital experience with sequential CMF chemotherapy followed by radiation in the adjuvant therapy of stage I and stage II breast cancer we reviewed the records of patients at our center. This group of 34 patients was treated in a homogenous manner, all receiving standard CMF for six cycles followed by radiotherapy after lumpectomy with axillary lymph node dissection. The radiation course was 5040cGy to the entire breast (28 fractions in 45 elapsed days) followed by a boost to the tumor site of 1800cGy in 10 fractions. Thirty-four patients were identified and followed for an average of 5 years (range 1.5–11.5 years). One patient had local recurrence and with subsequent treatment is disease-free at 5 years postrecurrence (8 years from initial diagnosis). Two deaths were not breast-cancer related (1 myocardial infarction at year 3, 1 melanoma at year 7.5). The estimated probability of no relapse at 5 years and 8 years by Kaplan-Meier analysis is 79% and 60% respectively. Overall and disease-free survival in this group of patients treated with breast-conserving surgery and CMF chemotherapy followed by radiation is excellent. There appears to be no detriment to delaying radiotherapy until full doses of systemic treatment are given as local recurrence was rare (6%) and was amenable to further treatment.     

Autosomal recessive blepharoptosis,cleft lip/palate,dental anomalies,and ectrodactyly

Fluorescence in situ hybridization (FISH) with α-satellite DNA probes was used to study whole-arm chromosome translocation products in a family in which the propositus was shown to have a monosomy 18p/trisomy 20p imbalance. By this approach, we show that the chromosome 18 α-satellite DNA block is split into 2 smaller units, whereas the chromosome 20 breakpoint is not included within the α-satellite DNA region. We found no evidence to suggest that this split α-satellite DNA region has reduced or impaired the function of the centromere or that it contributed to the phenotype of the propositus. The FISH technique critically demonstrated the involvement of a whole-arm translocation in this case and provided accurate identification of breakpoints, which was not possible with standard banding techniques. © Wiley-Liss, Inc.     

Substance P augments the rate of vasodilation induced by calcitonin gene-related peptide in porcine ophthalmic artery in vitro.

Peptides may function as neurotransmitters liberated antidromically by sensory nerve fibres, provoking vascular responses having potential importance in some neurological disorders. Dose-response relaxation curves induced by substance P (SP) and calcitonin gene related peptide (CGRP) have been studied in porcine ophthalmic arteries in vitro. Both peptides induced vasodilation when tested separately (CGRP much greater than SP). Because of the putative interactions between such peptides in this vascular territory, a computerised system was also used for analysing over time the response to a single addition of either 10(-8) M CGRP, 10(-8) M SP or a combination of 10(-8) M SP + 10(-8) M CGRP. SP did not augment the maximum relaxation induced by CGRP alone, but increased significantly the rate of relaxation during the initial phase of the response. The effect induced by the SP+CGRP combination was stronger than the sum of the individual SP and CGRP-induced relaxations during the first 4 min of the response, which suggests a SP-CGRP synergism in this artery.