Botulinum toxin A for chronic daily headache: a randomized, placebo-controlled, parallel design study.

Sixty patients with headaches of more than 15 days per month were recruited for this double-blind, placebo-controlled, parallel study of botulinum toxin type A (BTX) for chronic tension type and chronic migraine headaches. The primary efficacy point was the number of headache-free days as assessed by diary for 12 weeks after BTX injection. Secondary efficacy points included global impressions, the use of abortive headache medications, and palpation. After recruitment, subjects kept diaries for 4 weeks prior to randomization, at which time they received either 200 U of BTX or matching placebo and were followed. After the week-12 evaluation, patients were offered 200 U of BTX (open label), and were similarly followed for another 12 weeks. The mean days with headache of the 60 subjects (49 female, mean age 47 +/- 11 years) was 23 +/- 7 out of 30. Both groups were demographically similar (58 completed). Over a 12-week period after injections, headache-free days had improved in the BTX group from week 8 to 12 (P < 0.05), and strongly tended to improve over the entire 12-week period, 33 +/- 23 vs. 24 +/- 16 days without headache (P = 0.07), but did not meet the a priori significance criteria. The subject global impressions (P < 0.05), subject change in headache impressions (P < 0.005), and investigator global impressions (P < 0.001) all improved in the BTX group compared with placebo. Adverse events were mild and did not differ between groups. At week 24 (open label), headache-free days were less in the twice BTX injected group compared with the once injected group, 40 +/- 26 vs. 26 +/- 19 (P < 0.05). BTX may help chronic daily headache and appears to have a cumulative effect with subsequent injections. The treatment was very well tolerated.

Quality and liability issues with the Papanicolaou smear: lessons from the science of error prevention.

The pathologists and cytologists who study Papanicolaou smears perform a highly successful cancer screening test in a low-prevalence population. This leads to a mathematically inevitable false-negative error rate even in the most competent professional hands. The US judicial system supports a public expectation of perfect performance by civil and, recently, criminal punishment of error. Lessons are sought from a considerable industrial experience with accident prevention for possible insights into process improvement that might mitigate the risk of false-negative errors. The elements that, by system analysis, contribute to accidents are reviewed, and the conditions that enhance the accident potential are outlined. The cognitive functions and aberrations that are involved in the operator component of error analysis are described. As a result of pathologists' activities in the systematic measurement of laboratory performance for the last half century, the College of American Pathologists' accreditation program and its derivative Clinical Laboratory Improvement Act requirements have already laid out the avenues of error minimalization. There are no lessons from the science of error prevention that can affect the public expectation of zero error in a screening test and the consequent punishment of cytology professionals. A thesis is offered that the problem is society's if its goal is eradication of cervical cancer mortality. A call is made for leadership by a prestigious, nonpathologist, national organization to make the public understand that the current cytology liability issue is primarily a threat to women and the public health. To initiate public dialogue, a mechanism is suggested to protect simultaneously a patient's right of access to the judicial system and the general availability of the Papanicolaou smear to reduce cervical cancer mortality and morbidity.

The pathology of regulation.

Clinical pathology officially began when inquisitive physicians in the nineteenth century sought explanations for the diseases they observed in their patients. The increasing application of the basic sciences to patients required physicians to spend more time and energy in the laboratory than with their patients. Methodology followed new technologic innovations that the profession began to critically review in the late 1940s. Initially, government involvement in laboratories was minimal and supportive. The role of the government evolved over the last decades from a patron of learning to a purchaser of a regulated commodity and paralleled the changing role of the clinical laboratory from medical practice to big business.

Intraoperative radioimmunodetection of ovarian cancer using monoclonal antibody B72.3 and a portable gamma-detecting probe.

To assess the value of radioimmunoguided surgery in the intraoperative detection of ovarian cancer, we used monoclonal antibody B72.3, radiolabeled with 125I, and a hand-held gamma-detecting probe in 13 women with ovarian cancer undergoing exploratory laparotomy. B72.3, which recognizes a tumor-associated glycoprotein, TAG 72, was injected 12-29 days preoperatively (intraperitoneally in four cases, intravenously in nine, and by both routes in one). Intraoperatively, the abdomen was surveyed with the probe and probe counts were correlated with biopsies and excised specimens studied by routine histologic stains. Probe counts were positive in four of seven evaluable patients with histologically confirmed disease. In three of these four patients, the probe detected cancer in specimens interpreted as normal on frozen histologic sections. The probe also identified microscopic cancer in the one patient who had no gross disease. The specificity of the probe was 70%. Preoperative computed tomography was normal in all patients, including those with tumors as large as 3 cm. This pilot study shows the ability of radioimmunoguided surgery to detect occult ovarian cancer.

Physician referral patterns for stutterers.

Many children who stutter initially seek guidance from their pediatricians. Pediatricians often do not refer stutterers for speech therapy. We present a brief analysis of pediatricians' views regarding stuttering, as well as their exposure to patients who stutter. We present a practical approach to children who stutter.

Nuclear magnetic resonance diagnosis of an anaplastic astrocytoma.

A patient presented with an 8-month history of a progressive left homonymous visual field deficit, left hemiparesis, and a left thalamocortical sensory deficit that was not detectable by repeated conventional neurodiagnostic evaluations. Proton nuclear magnetic resonance (NMR) imaging revealed a right parietal lesion characterized by a prolonged T2 (spin-spin relaxation time). At surgery, the mass proved to be an anaplastic astrocytoma. NMR appears to be more sensitive than x-ray computerized tomography scanning in some patients with malignant gliomas and offers the clinician an additional probe with which to evaluate these patients.

Nuclear magnetic resonance evaluation of stroke. A preliminary report.

Nine patients who had acute and subacute stroke were examined by nuclear magnetic resonance (NMR) using a 6-MHz Bruker Instruments proton scanner. A modified Carr-Purcell-Meiboom-Gill pulse sequence was used for signal detection. The resultant string of spin-echoes was Fourier transformed into projections that were subsequently back-projected to a series of spin-echo images. From these images, spin density and T2 were calculated for each pixel. The NMR scans revealed stroke in each of the patients, while CT demonstrated only eight of the lesions. T2 was prolonged in all of the ischemic regions and is the most sensitive NMR parameter in detecting stroke. These preliminary results suggest that NMR scanning of patients who have acute stroke may be clinically useful, and that the T2 component of the NMR signal is most important.

Quality assurance in surgical pathology--personal and peer assessment.

A mechanism for quality assurance in surgical pathology based on a review of the surgical pathology reports is described. The setting up of performance standards by the participating pathologists before the institution in quality assurance helped in acceptance of the critique of the reviewer. Suggestions are made to improve the quality of the surgical pathology report by incorporating the needs of th surgeons and oncologists, in the hope that the quality assurance process becomes oriented to patients care.

Haemorrhagic complications of multiple sclerosis.

Neurological exacerbations in multiple sclerosis patients are usually attributed to relapses of the disease. This report emphasises that other conditions, such as spontaneous CNS haemorrhage, may be responsible for the clinical deterioration. We describe two patients appropriately diagnosed as having multiple sclerosis who developed spontaneous CNS haemorrhage.