Hemoglobin Zurich. I. A New Hemoglobin Anomaly Associated with Acute Hemolytic Episodes with Inclusion Bodies after Sulfonamide Therapy

A new abnormal hemoglobin was observed in 15 members over four generations of a large Swiss family and has been termed "Hemoglobin Zürich."The discovery of this hemoglobin was prompted by a severe hemolytic crisisin two members of the family after sulfonamide therapy. During this episode,virtually all erythrocytes and reticulocytes contained a single large inclusionbody which was visible with Giemsa and brilliant cresyl blue stains. Outsidethe hemolytic episode, the erythrocytes revealed no morphologic abnormalities.The results of enzyme studies were all within normal limits. The associationof a hemoglobinopathy with a drug-induced inclusion body anemia withoutany demonstrable enzyme defect is a new entity. The anomalous hemoglobinis inherited as a dominant character and affects both sexes. Thus far, onlythe heterozygous form has been observed.

Submitted on April 9, 1962 Accepted on June 20, 1962     

Clinical Studies with Vincristine

Forty patients with malignant neoplastic disease received vincristine in aneffort to define the toxicity, the tolerated dose, the effect of varying doseschedules, and the antitumor properties. The toxicity of vincristine is doserelated, and the tolerated dose for the weekly schedule is 0.05 mg. per Kg.for the majority of patients. The tolerated dose per unit time is independentof the schedule of administration. The toxic manifestations relate primarilyto the neuromuscular system and the gastrointestinal tract. At the tolerateddose or below, these manifestations are reversible and not accumulative.Hematologic toxicity is rare, and thrombocytosis occurs in some patients.Vincristine produces tumor regression in the majority of the patients withlymphoma where its activity compares favorably with that of the alkylatingagents and vinblastine. There is suggestive evidence that cross-resistance between vincristine and the alkylating agents and between vincristine and vinblastine does not occur.

Accepted on December 28, 1962     

HEMOGLOBIN-OXYGEN AFFINITY IN HYPOPHOSPHATEMIC RICKETS

Abstract. In 14 patients with simple X–linked hypophosphatemic rickets, 5 were below the third percentile in height and 9 were between the third and twenty-fifth percentile. Although the mean serum inorganic phosphorus level was only 2.01±0.65 (normal range for all age groups is 3.8 to 6.0 mg/100 ml), both the mean values for red cell 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) were normal at 4.78±1.23 and 1.02±0.17 μmol/ml of red blood cells respectively. Moreover, the mean P₅₀ value was normal at 26.4±0.9 mmHg. These normal oxygen transport data make unlikely any proposal that short stature seen in these patients is secondary to chronic tissue hypoxia. They also indicate that the intra-erythrocytic organic phosphate levels are maintained at normal levels despite profound chronic hypophosphatemia.     

Respiratory sinus arrhythmia, cardiac vagal tone, and respiration: Within- and between-individual relations

Respiratory sinus arrhythmia (RSA) is frequently employed as an intra- and interindividual index of cardiac parasympathetic tone, although the relationship of RSA to interindividual differences in cardiac vagal tone remains questionable. Our study examined between- and within-subject relations among RSA, cardiac vagal tone, and respiratory parameters. Twenty-nine young adults performed two sessions of tasks under no medication and single and double autonomic blockade (intravenously administered propranolol and atropine). Parasympathetic tone was determined from heart period responses to complete vagal blockade. Results indicated the following. Resting RSA does not accurately predict individual differences in cardiac vagal tone. However, RSA and heart period together do predict such individual differences reasonably well. The relationship between individual variations in RSA and vagal tone is not improved by controlling respiratory parameters. Substantial cardiac vagal activity occurs during inspiration, and intraindividual variations in respiratory measures confound the association between RSA and cardiac vagal tone.     

A POSTOPERATIVE PROGNOSTIC NOMOGRAM FOR RENAL CELL CARCINOMA

PURPOSE: Few published studies have combined prognostic factors to predict the likelihood of recurrence after surgery for renal cell carcinoma. We developed a nomogram for this purpose. MATERIALS AND METHODS: With Cox proportional hazards regression analysis, we modeled pathological data and disease followup for 601 patients with renal cell carcinoma who were treated with nephrectomy. Predictor variables were patient symptoms, including incidental, local or systemic, histology, including chromophobe, papillary or conventional, tumor size, and pathological stage. Treatment failure was recorded when there was either clinical evidence of disease recurrence or death from disease. Validation was performed with a statistical (bootstrapping) technique. RESULTS: Disease recurrence was noted in 66 of the 601 patients, and those in whom treatment was successful had a median and maximum followup of 40 and 123 months, respectively. The 5-year probability of freedom from failure for the patient cohort was 86% (95% confidence interval 82 to 89). With statistical validation, predictions by the nomogram appeared accurate and discriminating with an area under the receiver operating characteristic curve, that is a comparison of the predicted probability with the actual outcome of 0.74. CONCLUSIONS: A nomogram has been developed that can be used to predict the 5-year probability of treatment failure among patients with newly diagnosed renal cell carcinoma. The nomogram may be useful for patient counseling, clinical trial design and patient followup planning.     

Surgical versus non-surgical endodontic re-treatment for periradicular lesions

Background : Though success rates of endodontic initial treatment have been improving over the years, persistence of periapical disease is far from being a rare condition. The most common therapeutical options for the re‐treatment of teeth with periapical pathosis are non‐surgical orthograde treatment and surgical treatment. Selection between alternative treatments should be based on assessment of respective benefits (mainly healing) and risks from studies consistent with a high level of evidence. Objectives : To test the null hypothesis of no difference in outcome between surgical and non‐surgical therapy for endodontic re‐treatment of periradicular lesions. Search strategy : The Cochrane Oral Health Group Trials Register, CENTRAL, MEDLINE and EMBASE were searched with appropriate search strategies. Handsearching included eight dental journals. The bibliographies of relevant clinical trials and relevant articles were checked for identifying studies outside the handsearched journals. Seven manufacturers of instruments in the field of endodontics or endodontic surgery or both, as well as the authors of the identified randomized controlled trials (RCTs) were contacted in order to identify unpublished or ongoing RCTs. No language restriction was placed. The last electronic search was conducted on 3rd April 2007. Selection criteria : All RCTs about re‐treatment of teeth with periapical pathosis in which both surgical and non‐surgical approaches were used and having a follow up of at least 1 year were considered for the analysis. Data collection and analysis : A quality assessment of the included RCTs was carried out and the authors were contacted for missing information. We independently extracted the data in duplicate. We followed the Cochrane Oral Health Group's statistical guidelines. Main results : Three RCTs were identified, two of them reporting different data from the same clinical study. The risk of bias was judged as moderate for one study and high for the other one. One hundred and twenty‐six cases were followed up for at least 1 year, and 82 had a follow up of 4 years. At the 1‐year follow up the success rate for surgical treatment was slightly better than non‐surgical (risk ratio (RR) 1.13; 95% confidence interval (CI) 0.98 to 1.30). When the follow up was extended to 4 years (only one RCT made it) the outcome for the two procedures became similar. Authors' conclusions : The finding that healing rates can be higher for cases treated surgically as compared to those treated non‐surgically, at least in the short term, is based on two RCTs only. A single RCT reported that in the medium to long term healing rates for the two procedures are very similar. There is currently scarce evidence for a sound decision making process among alternative treatments for the re‐treatment of a periradicular pathosis. More well‐designed RCTs should be performed with follow up of at least 4 years, and with a consistent sample size, to detect a true difference in the long term between the outcomes of the two alternative treatments, if any exist.     

Surgical Excision versus Curettage plus Cryosurgery in the Treatment of Basal Cell Carcinoma

BACKGROUND: Both cryosurgery, with and without prior curettage, and surgical excision (SE) are common therapeutic strategies for basal cell carcinoma (BCC). OBJECTIVE: The objective was to compare the efficacy between curettage plus cryosurgery (C&C) and SE in nonaggressive BCC of the head and neck. MATERIALS AND METHODS: A randomized controlled trial was carried out, in which tumors were assigned to either C&C (n=51) or SE (n=49). C&C was performed with a double freeze-thaw cycle after prior curettage of the tumor. SE was performed with a margin of 3 mm and with delayed histologic examination. RESULTS: Recurrences occurred 9 times after C&C (17.6%) and 4 times after SE (8.2%). The overall 5-year recurrence probability was 19.6% for C&C and 8.4% for SE (p=.10). A hazard ratio of 2.57 (95% CI, 0.79-8.34) indicated a putative, but not statistically significant, advantage of SE. CONCLUSION: These data reflect the outcome of the first randomized controlled trial with long-term follow-up in the treatment of BCC, comparing C&C with SE. Although not statistically significantly different, the observed differences could still be of clinical relevance. Owing to the trend toward lower recurrence rates, better cosmetic results, and reduced wound healing time, we believe that SE should be preferred to C&C in the treatment of primary, nonaggressive BCC of the head and neck.