Solitary bronchioloalveolar carcinoma: CT criteria

The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis.     

Abnormal electroretinography in schizophrenic patients with a history of sun gazing.

Electroretinographic (ERG) measurements were performed in 9 schizophrenic patients and in 13 control subjects. The measurements of schizophrenic patients as a group did not differ from those of normals. However, 6 schizophrenic patients who had a past history of sun gazing showed a decrease in retinal responsiveness under conditions of light adaptation. These results suggest that a subgroup of schizophrenic patients, who show deviant light-related behavior, have abnormal ERG. We postulate that an abnormality in retinal dopaminergic neurons, which are known to reduce light responsiveness of horizontal and ganglion cells, is the underlying pathophysiology of this clinical finding.     

Perception and social consequences of tuberculosis: A focus group study of tuberculosis patients in Sialkot, Pakistan

Treatment defaulting is one of the major causes of the failure of TB control programs. In Bethania Hospital. Sialkot, defaulting rates are high: 72% for the standard 12 months course and 56% for the 8 months course. Attrition is especially important in the first weeks of treatment: < 70% of the patients start the 10th week of treatment. A focus group discussion study has been carried out to gain a better understanding of the impact of social stigmatization, treatment cost and pregnancy on defaulting. The study population consisted of 3 male and 3 female groups each with 8 hospitalized TB patients. The study shows that TB is perceived as a very dangerous, infectious and incurable disease. This perception has many social consequences: stigmatization and social isolation of TB patients and their families; diminished marriage prospects for young TB patients, and even for their family members; TB in one of the partners may lead to divorce. Due to fear patients often deny the diagnosis and reject the treatment. While both male and female TB patients face many social and economical problems, female patients are more affected. Divorce and broken engagements seem to occur more often in female patients. Females are usually economically dependent on their husbands and family in law, and need their cooperation to avail of treatment. The belief that pregnancy enhances the risk for relapse decreases their marriage prospects. Pregnancy is also a reason for stopping TB treatment as both are considered as incompatible. The findings of this study reveal the urgent need for a health education campaign to convince the general population that tuberculosis is curable. All health care providers should act as destigmatizers.     

The need for future surgical low rectal cancer studies

Optimal surgery remains the mainstay of best outcome for rectal cancer. The demonstration, during the 3rd Annual Pelican Surgical Workshop Symposium, of an abdomino‐perineal excision (APE) performed in the ‘Berlin position’, further added to the debate on optimal surgical technique. Much interest was created at the 1st Pelican symposium with the demonstration, by the Swedish surgeon Dr Torbjorn Holm, of a prone APE and the delivery of a ‘cylindrical’ specimen and the potential to reduce local recurrence using this approach. The high rates of local recurrence following APE and the discussions as to optimal technique have led to the development of a proposed MERCURY Study Group study to assess the benefit of a radical APE, with careful assessment of the impact that this operation may have on morbidity. A German study has also been proposed adopting the UK's multidisciplinary team approach. It aims at targeting preoperative chemoradiotherapy at those patients in whom a radical APE or total mesorectal excision is likely to result in an involved surgical resection margin. In this article we review the evidence for improving the surgical technique for low rectal cancer. We believe improvements may be best achieved through continued European prospective, multi‐centre, multidisciplinary studies.     

Macroscopic geometric heterogeneity effects in radiation dose distribution analysis for boron neutron capture therapy.

Calculations of radiation flux and dose distributions for boron neutron capture therapy (BNCT) of brain tumors are typically performed using sophisticated three-dimensional analytical models based on either a homogeneous approximation or a simplified few-region approximation to the actual highly heterogeneous geometry of the irradiation volume. Such models should be validated by comparison with calculations using detailed models in which all significant macroscopic tissue heterogeneities and geometric structures are explicitly represented as faithfully as possible. This paper describes such a validation exercise for BNCT of canine brain tumors. Geometric measurements of the canine anatomical structures of interest for this work were performed by dissecting and examining two essentially identical Labrador retriever heads. Chemical analyses of various tissue samples taken during the dissections were conducted to obtain measurements of elemental compositions for the tissues of interest. The resulting geometry and tissue composition data were then used to construct a detailed heterogeneous calculational model of the Labrador head. Calculations of three-dimensional radiation flux distributions pertinent to BNCT were performed for this model using the TORT discrete-ordinates radiation transport code. The calculations were repeated for a corresponding volume-weighted homogeneous-tissue model. Comparison of the results showed that peak neutron and photon flux magnitudes were quite similar for the two models (within 5%), but that the spatial flux profiles were shifted in the heterogeneous model such that the fluxes in some locations away from the peak differed from the corresponding fluxes in the homogeneous model by as much as 10%-20%. Differences of this magnitude can be therapeutically significant, emphasizing the need for proper validation of simplified treatment planning models.     

The striatal-enriched protein tyrosine phosphatase gates long-term potentiation and fear memory in the lateral amygdala.

BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders.     

Antiinflammatory agents. 4. Syntheses and biological evaluation of potential prodrugs of 2-amino-3-benzoylbenzeneacetic acid and 2-amino-3-(4-chlorobenzoyl)benzeneacetic acid

A series of potential prodrugs of 2-amino-3-benzoylbenzeneacetic acid (amfenac) and 2-amino-3-(4-chlorobenzoyl)benzeneacetic acid were synthesized and evaluated for their cyclooxygenase inhibiting properties, antiinflammatory potency, and gastrointestinal irritation liability. One compound, 2-amino-3-(4-chlorobenzoyl)benzeneacetamide, possessed a therapeutic index 1 order of magnitude greater than that of indomethacin.     

A dideazatetrahydrofolate analogue lacking a chiral center at C-6, N-[4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl]benzoyl]-L-glutamic acid, is an inhibitor of thymidylate synthase.

N-[4-[2-(2-Amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl]benzoyl]-L-glutamic acid (15), prepared in five steps from 2-pivaloyl-7-deazaguanine, has been found to be an antitumor agent with its primary site of action at thymidylate synthase rather than purine synthesis. This compound appears to be a promising candidate for clinical evaluation.     

Rapid sequence treatment of advanced squamous cell carcinoma of the upper aerodigestive tract: A pilot study

A review of the literature suggested that prolonged treatment time may lessen the probability of cure for patients with advanced squamous cell carcinoma of the upper aerodigestive tract. To shorten treatment time, rapid sequence treatment (RST) was devised in which chemotherapy, surgery, and irrada-tion were administered in a total treatment time of 8 weeks. Twelve patients were treated and followed 3 years or longer. Medical complications were minor. Osteonecrosis occurred in each of the first five patients and was the only major complication of the protocol. Surgical techniques were modified, and no additional patient developed osteonecrosis. No patient developed local or regional recurrence. Two patients developed distant metastases and three other patients developed second primaries. Absolute survival was 50%. Rapid sequence treatment is an aggressive and potentially hazardous protocol that yielded encouraging results in this pilot study.     

Injury of rat renal vessels following extracorporeal shock wave treatment.

The locations of extracorporeal shock wave treatment induced renal vascular injury and the sources of significant renal hemorrhage were determined in a rat model by means of two different vascular casting procedures. Silicone-rubber injected vascular preparations for light microscopy or corrosion casts for scanning electron microscopy were made following gross examination of the treated organs and their contralateral controls. After 1000 shock waves at 18 kV, five out of 20 treated kidneys appeared to be normal or minimally affected, while 15 showed gross evidence of marked vascular injury. Gross interstitial hemorrhage (15/20), subcapsular hematomas (7/20), and hemorrhages into the renal pelvis (5/20) were confirmed by extravasations of casting materials. These could be traced back to their vascular sources in several instances. Disruptions of interlobar and arcuate veins gave rise to most significant interstitial, subcapsular, and renal pelvic extravasations. On a microscopic scale cortical venules were among the most frequently injured vessels. The arterial vasculature was not spared. Arterial injury ranged from complete arcuate occlusion to small afferent arteriolar and glomerular capillary extravasations. The significance of shock wave induced vascular injury is discussed with respect to potential clinical side effects of ESWL.