A polymerase chain reaction study of the stability of Ig heavy-chain and T-cell receptor delta gene rearrangements between presentation and relapse of childhood B-lineage acute lymphoblastic leukemia

Ig heavy-chain (IgH) and partial V delta 2-D delta 3 T-cell receptor (TCR) gene rearrangements were investigated, by polymerase chain reaction (PCR) amplification and sequence analysis, in 52 patients at presentation and first relapse and in 14 at both first and second relapse of B-lineage acute lymphoblastic leukemia. In combination, these techniques amplified one or more clonal markers at presentation in 90% of patients (IgH-PCR, 75%; V delta 2-D delta 3-PCR, 46%; both, 33%). Changes in the pattern of amplification between presentation and first relapse were seen in 31% of patients positive by IgH-PCR at presentation and in 25% of those positive by TCR delta-PCR. Only 3 patients showed complete change in their rearrangements, which is suggestive of relapse with a new clone. Furthermore, despite the high reported rates of oligoclonality and clonal evolution at the IgH locus, the results presented show that false-negative minimal residual disease (MRD) detection can be avoided by designing D-N-J probes to all presentation rearrangements. Using a PCR approach for both gene markers, false-negative testing because of clonal evolution would have only occurred in 3 (8%) of the IgH-positive patients, in contrast to 5 (21%) of V delta 2-D delta 3-positive patients. Combining these two systems increases the proportion of patients open to study to 90%, allows comparative studies of the sensitive of the two methods, and reduces the rate of false-negative assessment of MRD caused by clonal evolution to less than 10%. We conclude that large prospective PCR studies of MRD detection should examine gene rearrangements at multiple loci to maximize their applicability and to minimize false-negative relapse prediction.     

Stage IB,IIA and proximal IIB,carcinoma of the uterine cervix,treated by irradiation alone or in combination with surgery

This is a report of a nonrandomized comparison of treatment results of 139 patients with stage IB, IIA and proximal IIB carcinoma of the uterine cervix treated by radiation alone and 113 treated with a combination of radiation and surgery. The five-year tumor free acturial survival for the patients with stage IB either with irradiation alone (RT) or combined with surgery (RS) was approximately 87%. For stage II the tumor free actuarial five-year survival 79% with patients of RS, and 76% with RT. In the 113 patients treated with RS there were 18 (16%). In the 139 patients treated by RT there were 18 (13%) recurrences of pelvic, 4 local recurrences, 11 combined with parametrial, and free parametrial recurrences. There was no significant difference in the survival and recurrence rate of the patients treated with either method. Major complications were comparable in both groups (RT approximately 25% and RS approximately 10%), but 2/3 of those complications recovered without sequelae. The most frequent minor complication in the patients treated with RT was rectosigmoiditis.     

Proarrhythmic effects of a quinidine analog in dogs with chronic A-V block

Summary— The proarrhythmic effects of 3-hydroxy-hydroquinidine (3-OH-HQ) and quinidine were compared in a canine model of QT-dependent ventricular arrhythmias. Eight hypokalemic ([K+] ≤ 3.2 mmol/l) dogs with AV block (around 45 bpm) were given either drug in a randomized order at 2-day intervals. Each drug was given as two 1 hour doses, with a bolus (low dose: 5 mg/kg or high dose: 10 mg/kg) plus infusion (25 or 50 μg/kg/min) protocol. Propranolol infusion was combined with a third hour of the high dose infusion. Electrophysiologic measurements were performed at baseline and 30 minutes after the beginning of each dose and propranolol infusion, and proarrhythmic events were recorded 30 minutes before and during the experiment. Neither drugs altered the ventricular cycle length. Quinidine and 3-OH-HQ prolonged the QT interval similarly and significantly when paced at 60 bpm after the low dose (+ 39 ± 18 and + 28 ± 22 msec, respectively) and after the high dose (+ 51 ± 29 and + 50 ± 22 msec). Quinidine was more arrhythmogenic than 3-OH-HQ: 7/8 dogs (p ≤ 0.05) developed ventricular arrhythmias (isolated, repetitive ventricular beats, or polymorphic ventricular tachycardias) during quinidine infusion (low dose: 4 dogs) compared to 3/8 dogs (NS) during 3-OH-HQ infusion (low dose: 1 dog). Addition of propranolol-induced bradycardia (around 30 bpm) caused torsades de pointes (wave burst arrhythmias) or polymorphic ventricular tachycardias after both drugs (in 3 dogs after quinidine and in 2 dogs after 3-OH-HQ). Thus 3-OH-HQ was slightly less arrhythmogenic than quinidine in this model of torsades de pointes, but the addition of an extra favouring factor (bradycardia) reduced that difference.     

Cerebrospinal fluid shunts: flow measurements with MR imaging

The authors describe a technique for determination of shunt patency by quantifying cerebrospinal fluid shunt flow rates with magnetic resonance (MR) imaging. This method uses a modified clinical sequence that is both sensitive to slow flow perpendicular to the imaging plane and capable of achieving oblique angles with a 4-cm field of view. Velocity-dependent phase images were used to quantify flow rates within the shunt. A preliminary study was performed in seven patients with hydrocephalus and cerebrospinal fluid shunts. Two patients were found to have zero flow in the shunt, while the remaining five had flow rates ranging from 4 to 19 mL/h. Results showed that the measurement of flow rates within the shunt lumen with MR imaging is clinically feasible.     

Percutaneous cholecystolithotomy: preliminary experience

Percutaneous removal of gallstones was employed as the definitive form of therapy in three patients with acute cholecystitis. Percutaneous cholecystolithotomy may be an alternative form of therapy for selected patients with gallbladder calculi.     

Whole blood and plasma histamine in common migraine

Whole blood and plasma histamine levels were measured in 27 non-medicated patients with common migraine. In nine cases blood was drawn 1-2 h after the onset of a migraine attack. The whole blood histamine levels of migraineurs and controls did not differ significantly. In contrast, histamine levels were significantly increased in plasma from patients both during and between migraine attacks, as compared with controls (p less than 0.001). Finally, plasma taken from migraine patients induced a significantly greater release of histamine from control whole blood than did plasma taken from control subjects (p less than 0.01).     

Utilization of fine-needle aspiration biopsy in the diagnosis of metastatic tumors to the pancreas

There is relatively little information concerning the use of fine-needle aspiration biopsy (FNAB) to diagnose a mass in the pancreas that is secondary to metastatic tumor. This study reviews the incidence and types of neoplasms which metastasize to the pancreas and assesses the contribution FNAB can make in their diagnosis. of 117 radiologically guided FNABs of the pancreas, 11% (n = 13) showed metastatic malignancy. Nine patients had a previous history of malignancy while four patients presented with a pancreatic mass and were subsequently found to have widespread malignant disease. the majority of metastatic lesions were epithelial (77%, n = 10). Patient outcomes were generally poor (mean survival 2.8 mo). Metastases to the pancreas occur from a variety of primary sites and should be considered in patients with a pancreatic mass and a history of prior malignancy. FNAB is useful in diagnosing these metastases and this is clinically important because of their poor prognosis.