NEUROMUSCULAR REFRACTORINESS DURING BLOCKAGE OF TRANSMISSION: A quantitative study

The effects of suxamethonium and tubocurarine on the refractorinessof neuromuscular transmission were studied in 21 anaesthetizedadult subjects under various levels of neuromuscular block.The ulnar nerve was stimulated every 12 s with twin supramaximalstimuli 4 ms apart. At any level of block, the refractory fraction(the fractional decrement of the compound electromyographicresponse of the adductor pollicis to the second twin stimulus,relative to the response to the first) was used to quantifyneuromuscular refractoriness. The magnitude of block was determinedby the response to the first stimulus. Correlation between refractorinessand the degree of block was sought. Without block, neuromusculartransmission averaged 23% (SEM 4) refractory with this twininterval. The refractory fraction was increased markedly bysuxamethonium, reaching 0.69 (SEM 0.1) at 50% block. Completerefractoriness occurred during 25–75% block in eight of11 instances. Tubocurarine did not significantly alter refractoriness,paired responses to the twin stimuli decreasing proportionatelyduring block.     

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.     

The Psychological Impact of Implantable Cardioverter-Defibrillator Recalls and the Durable Positive Effects of Counseling

Background: It is known that patients with lifesaving devices such as implantable cardioverter-defibrillators (ICDs) may be alarmed and worried by recalls or alerts related to their ICDs.
Objectives: This study aimed to determine whether counseling has any short- or long-term benefits, and to look for characteristics that identify those most worried and those most in need of counseling.
Methods: Among 100 patients with recall or alert ICDs, 14 were pacer dependent; 50 had ICDs for 1° prevention and 22 were women. Patients completed a survey indicating how worried they were on learning of the recall or alert (0–10 scale). After counseling and advice in accordance with manufacturer guidelines, patients were asked to indicate their level of worry, and were again asked after 6 months.
Results: For all patients, the "worry level" at the initial interview was 5.0 ± 3.7, falling to 2.2 ± 3.0 after counseling (P < 0.001) and 1.4 ± 2.3 after 6 months (P < 0.001 vs both earlier levels). There were no significant differences between those implanted for 1° versus 2° prevention or for pacer dependency. Women were initially more worried than men, but not for the long term. The 49 patients whose ICDs could be managed by reprogramming or software fix had significant reduction in worry after counseling and at 6 months compared to others. The 18 patients recommended for operative intervention remained more concerned after counseling (3.5 ± 3.3 vs 1.9 ± 2.9, P = 0.043).
Conclusions: Patients' concerns resulting from ICD recalls or alerts can be reduced by appropriate counseling. Those patients whose ICDs could be reprogrammed to safer parameters had the most reduction in worry levels.     

Periodic courses of human 1–34 parathyroid peptide alternating with calcitriol paradoxically reduce bone remodelling in spinal osteoporosis

In an attempt to achieve an anabolic response in both axial and peripheral bone, we treated twelve patients with osteoporosis using human 1-34 parathyroid peptide given discontinuously. The peptide was given as seven daily subcutaneous injections followed by 21 days' treatment with 0.25 mg calcitriol orally. This regime was repeated cyclically for at least sixteen cycles, of which the first four were at a lower dose of hPTH 1-34 than used subsequently. The results of treatment were monitored by kinetic, densitometric, histomorphometric and biochemical studies performed before and during treatment. Two patients developed hPTH 1-34 binding in their plasma during treatment: this was presumed to be due to the development of antibodies. The remainder, instead of increasing their indices of bone turnover as judged by iliac bone histomorphometry, were found to have consistent reductions in trabecular resorption surfaces. The other indices of bone formation and resorption measured showed no change or comparable reductions. The small increases seen in total body calcium were consistent with 'in-filling' of deleted basic multicellular units (BMUs). Because there is no evidence that calcitriol alone causes comparable reductions in activation of bone remodelling in osteoporosis, interruption of treatment with hPTH 1-34 after 7 days may have led to a failure of the activation mechanism to proceed to the resorption stage, with a consequent overall reduction in remodelling activity. This type of treatment regime, with its calcitonin-like effect, might be effective in reducing net bone loss due to imbalance between bone formation and resorption at the BMU level, particularly in patients with increased numbers of BMUs ('high turnover' osteoporosis).(ABSTRACT TRUNCATED AT 250 WORDS)     

Adult xanthogranulomatosis associated with abnormal plasma apolipoprotein levels

A case of adult xanthogranulomatosis was investigated in depth for lipid abnormalities. The xanthogranulomatous lesion was shown to be composed primarily of cholesterol esters and triglycerides. Fasting plasma lipid levels and lipoprotein concentrations were within normal limits. Plasma lipoprotein electrophoresis and immunoelectrophoresis demonstrated normal high-density lipoprotein (HDL) and low-density lipoprotein mobilities. Polyacrylamide-gel isoelectric-focusing electrophoresis revealed increased levels of very-low-density apolipoprotein (apo) E, especially apo E-III. In the HDL fraction, apo-C-III and apo-E levels were both found to be slightly elevated. These findings might imply a causal relationship between the abnormal plasma apolipoprotein levels and the xanthogranulomatous disease.     

Species Differences in Susceptibility to 1,3-Dinitrobenzene-lnduced Testicular Toxicity and Methemoglobinemia

The testicular toxicity and methemoglobinemia induced by 1,3-dinitro-benzene(1,3-DNB) was compared in two species, the Sprague-Dawley ratand the golden Syrian hamster. A marked difference in susceptibilityto both endpoints of toxicity was observed. The hamster showedno testicular lesions at dose levels up to 50 mg/kg whereas,as previously reported by others, damage to rat testicular tubulesin later stages of spermatogenesis was readily apparent at a25 mg/kg dose level. Similarly, administration of 1,3-DNB inducedsubstantially less methemoglobinemia in the hamster than inthe rat. For example, at the 25 mg/kg dose level peak levelsof methemoglobin in the hamster were 15% compared with 80% inthe rat. Mortality in the rat also occurred at lower doses thanin the hamster (50 vs 100 mg/kg, respectively). In in vitrostudies,the capacity of 1,3-DNB and 1,3-DNB metabolites (nitroaniline,nitroacetanilide, aminoacetanilide, diacetamidobenzene) to inducemethemoglobinemia was examined in suspensions of red blood cellsobtained from both species. Only 1,3-DNB caused the formationof methemoglobin and rat red blood cells were twice as sensitiveas hamster red blood cells. The species difference in susceptibilityto both methemoglobinemia and testicular toxicity could indicatedifferences in 1,3-DNB clearance and/or formation of toxic metabolites.Additional metabolic work is under way. This study demonstratesthat the hamster is more resistant than the rat to the testicularlesion and methemoglobinemia induced by 1,3-DNB. c 1991 Societyof Toxicoiofy.     

Prevalence of factor IX inhibitors among patients with haemophilia B: results of a large-scale North American survey

Summary. This survey provides new information on the severity of factor IX deficiencies among patients being treated for haemophilia B and on the prevalence of factor IX inhibitors in this population. A questionnaire was sent to 150 haemophilia treatment centres in the United States and Canada. 82 centres responded and provided data on 1967 patients with haemophilia B. 37% of these patients had severe haemophilia B (<1% of the normal level of factor IX), 33% had moderate haemophilia B (1–5% of the normal level of factor IX), and 30% had mild haemophilia B (>5% of the normal level of factor IX). Only 29 (1.5%) of the patients had factor IX inhibitors; 28 of these patients (96.6%) had severe haemophilia B, and one of these patients (3.4%) had moderate haemophilia B. Factor IX inhibitor titres were 0.6–1 Bethesda unit (BU) in seven patients, > 1–5 BU in four patients, > 5–10 BU in one patient, and > 10 BU in 17 patients. Factor IX inhibitors are much less common in patients with haemophilia B than in patients with haemophilia A.