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Re: Milton TM, Murray PG, Irvine GH, Use of a healing plate in establishing successful exposure of palatally impacted canines (Br J Oral Maxillofax Surg 2003;41:264-5).
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Pennsylvania Superior Court--AIDS: disclosure of physician's HIV status--in re Milton S. Hershey Medical Center.
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In re application of Milton S. Hershey Medical Center.
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In re Application of Milton S. Hershey Medical Center.
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"First do no harm...": can restrictions on HIV-infected health care workers be justified?
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Re: "Diet and nuclear lens opacities".
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Bordetella pertussis. A re-emerging pathogen in Virginia.
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Brain injury in boxing.
This lecture on activism via forensic medicine for the public good was given in honor of Milton Helpern. Boxing dates from antiquity but is now being re-evaluated as a viable part of civilized society. Chronic brain damage caused by repetitive subconcussive blows to the head has been shown to be present in 70-87% of boxers who had had many fights. A broad international medical consensus supports the view that boxing is medically and morally wrong and should be banned in civilized countries.
Plasmodium gallinaceum: clinical progression, recovery, and resistance to disease in chickens infected via mosquito bite.
Historically, in vivo experiments of Plasmodium gallinaceum in chickens have caused high mortality. Perhaps because of this high mortality, it remains to be demonstrated whether recovered birds will resist a second episode of illness when re-exposed to infected mosquitoes. In the current study, groups of 10 chicks were infected with P. gallinaceum via mosquito bite. Parasitemia and anemia were followed by recovery in all birds, although they had persisting, low levels of parasitized erythrocytes (0.007 +/- 0.019%). Twenty-three days after the initial exposure, 10 recovered chicks were rechallenged with P. gallinaceum via mosquito bite; none of them developed clinical or hematological evidence of malaria, in contrast to matched control birds, which all became diseased (P < 0.001). Unlike previous studies, the current experiment had no mortality in chickens infected with P. gallinaceum by mosquito bite. Recovered birds resisted disease from re-exposure to the same organism. The duration and nature of immunity or premunition remain to be determined.
Estrogen depletion differentially affects blood pressure depending on age in Long-Evans rats.
Normotensive female rats exhibit age-related decreases in estrous cyclicity and increases in blood pressure. In spontaneously hypertensive rats, estrogens, including dietary phytoestrogens, prevent or attenuate the increased blood pressure associated with estrogen depletion. The present studies examine the effects of ovariectomy (OVX) at either 3 or 10 mo of age. Although blood pressure increases from 3 to 9 mo, OVX at 3 mo of age has no added effect--despite the fact that OVX (compared to ovary-intact) rats weighed significantly more. In contrast, aging from 10 to 16 mo is associated with a further increase in blood pressure, which is potentiated by estrogen depletion. Removal of dietary phytoestrogens exacerbated the hypertensive effects of OVX in these middle-aged rats. As in younger rats, estrogen depletion at 10 mo of age was associated with greater weight gain. Whereas estrogen depletion at 3 mo of age was without effect on fluid intake over the next 6 mo, OVX at 10 mo of age was associated with decreased fluid intake. In a final study, rats were OVX at 3 mo of age with estradiol (E2) treatment initiated at 10 mo of age. Long-term OVX ( >10 mo) was associated with increased blood pressure and mortality at 14-16 mo of age. Circulating levels of E2 were decreased by OVX. Plasma aldosterone was increased by OVX, an effect which was prevented by either E2 or phytoestrogens. Neither E2 nor aldosterone was affected by age. These data indicate that (a) the physiological effects of estrogen depletion vary with age; (b) phytoestrogens in the diet exert some protective effects; and (c) long-term OVX in the absence of hormone re-placement is associated with premature mortality. We suggest that chronic increases in aldosterone and sympathetic tone underlie the hypertensive effects of estrogen depletion.
Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: a report from the National Wilms Tumor Study Group.
PURPOSE: NWTS-5 was a multi-institutional clinical trial for patients less than 16 years of age at diagnosis with specific renal neoplasms who were diagnosed between August 1, 1995 and May 31, 2002. A uniform approach to the treatment of patients with relapse was employed. PATIENTS AND METHODS: Seventy-two patients who relapsed after immediate nephrectomy (stages I and II), initial chemotherapy with vincristine (VCR) and actinomycin D and no radiation therapy were registered on stratum B of the NWTS-5 relapse protocol. Four patients were not evaluable: one due to insufficient data and three due to major protocol violations. Among the 68 remaining patients, one who was 19 years of age at initial diagnosis of Wilms tumor, five with bilateral Wilms tumor at diagnosis, three who developed a contralateral relapse, and one with persistent disease were not included in this analysis. Relapse treatment included surgical excision, when feasible, radiation therapy and alternating courses of VCR, doxorubicin and cyclophosphamide and etoposide and cyclophosphamide. RESULTS: The outcomes of 58 patients were analyzed. The lung was the only site of relapse for 31 patients. Event-free survival 4 years after relapse was 71.1% and 4-year overall survival was 81.8% for all patients and were 67.8 and 81.0% for those who relapsed only to their lungs. The most frequent toxicities were hematological. CONCLUSIONS: These results demonstrate that a significant proportion of children with Wilms tumor who relapse after initial treatment with VCR and actinomycin D can be successfully re-treated.
A working group classification of focal prostate atrophy lesions.
Focal atrophy is extremely common in prostate specimens. Although there are distinct histologic variants, the terminology is currently nonstandardized and no formal classification has been tested for interobserver reliability. This lack of standardization hampers the ability to study the biologic and clinical significance of these lesions. After informal and formal meetings by a number of the authors, focal atrophy lesions were categorized into 4 distinct subtypes as follows: (i) simple atrophy, (ii) simple atrophy with cyst formation, (iii) postatrophic hyperplasia, and (iv) partial atrophy. In phase 1 of the study, pathologists with varying levels of experience in prostate pathology were invited to view via the Internet a set of "training" images with associated descriptions of lesions considered typical of each subtype. In phase 2 of the study, each participant provided diagnoses on a series of 140 distinct "test" images that were viewed over the Internet. These test images consisted of the 4 subtypes of atrophy and images of normal epithelium, high grade prostatic intraepithelial neoplasia, and carcinoma. The diagnoses for each image from each pathologist were compared with a set of "standard" diagnoses and the kappa statistic was computed. Thirty-four pathologists completed both phases of the study. The interobserver reliability (median kappa) for classification of lesions as normal, cancer, prostatic intraepithelial neoplasia, or focal atrophy was 0.97. The median kappa for the classification of atrophy lesions into the 4 subtypes was 0.80. The median percent agreement with the standard diagnosis for the atrophy subtypes were: simple 60.6%, simple with cyst formation 100%; postatrophic hyperplasia 87.5%; partial atrophy 93.9%. The lower percentage for simple atrophy reflected a propensity to diagnose some of these as simple atrophy with cyst formation. Seven pathologists completed the phase 2 analysis a second time, and their intraobserver reproducibility was excellent. Three of 4 pathologists with low agreement with the standard diagnosis for simple atrophy improved their scores after repeating the analysis after re-examination of the "training set" of images. In conclusion, these criteria for variants of focal prostate atrophy may facilitate studies to examine the relation between various patterns of prostate atrophy and prostate cancer.
[Advances in necrotizing enterocolitis].
OBJECTIVE: To evaluate recently reported findings on necrotizing enterocolitis, Paying particular attention to pathogenesis, management and preventative strategies. DATA SOURCES: The articles covered in this report consist of randomized and quasi-randomized trials, case control studies, meta-analyses and reviews published recently. Certain other articles were also included because of their utmost importance to the subject. RESULTS: Necrotizing enterocolitis remains a major cause of morbidity and mortality in preterm infants. Those who are born with intra-uterine-growth retardation are at a several-fold increased risk. Possible pathophysiologic processes beginning in utero and continuing after birth are discussed in this review. Other factors involved in the process are related to the role of arginine and the production of intestinal nitric oxide and the action of epidermal growth factor in the regulation of cell regeneration. Perforated necrotizing enterocolitis is a complex surgical problem; definitive evidence-based guidelines for the best approach are yet to be determined. After surgery, although residual small bowel length and the presence of the ileo-cecal valve remain important predictors of duration of parenteral nutrition in infants, other factors, such as the early use of breast milk or amino acid-based formula, may also play a role in intestinal re-adaptation. Prevention strategies have centered on feeding practices and emerging experiments such as amino acid supplementation, are also discussed. CONCLUSION: Significant results in terms of mortality and morbidity will be achieved through better understanding of necrotizing enterocolitis pathogenesis and clinical and surgical management in addition to the employment of preventative strategies.
[Intravascular lymphoma treated with anti CD20 monoclonal antibodies. Report of one case].
We report a 78 year old male with prostatism, that was subjected to a prostate biopsy. The pathological study showed a microvascular lymphocytic infiltration. Four months later, the patients presented with reduced alertness, cough, dyspnea, fever and elevation of lactic dehydrogenase and erythrocyte sedimentation rate. Chest and abdominal CAT scans, bone marrow aspirate, protein electrophoresis and prostate specific antigen were normal. A re-evaluation of prostate biopsy showed an intravascular lymphoid infiltration, positive for CD45 and CD20, compatible with the diagnosis of intravascular lymphoma. Chemotherapy was started, but it was not tolerated by the patient and the response was partial. Therefore, treatment with monoclonal antibodies anti CD20 (Rituximab) was started. The tumor had a complete and prolonged (24 months) remission after the treatment
Measurement of excessive appetite and metabolic changes in Prader-Willi syndrome.
The behavioural, cognitive and metabolic response to food intake was studied in 13 adults with the Prader-Willi syndrome (PWS) and compared to ten age-matched controls. Rates of eating were observed during one hour's access to food and feelings of hunger were assessed using a visual analogue scale. Blood was taken for estimation of glucose, insulin, cholecystokinin (CCK), prolactin, growth hormone (GH) and cortisol every 20 min for a total period of 100 min. Ten (76%) of the subjects with PWS ate steadily for the whole hour that food was available and on average consumed three times more calories than the control group. The median ratings for feelings of hunger in the PWS group changed in the expected direction but these changes were delayed compared to the control group and only reached the same level as the controls after the PWS subjects had eaten a significantly greater amount of food. In the PWS group, in contrast to the control group, feelings of hunger started to re-emerge shortly after food was removed. There were marked differences between individuals with PWS in the extent of the changes in serum prolactin levels. Increases in plasma glucose levels were inversely correlated with changes in hunger ratings in the PWS group, but not the control group. There was a significantly greater increase in serum CCK levels during the meal in the PWS group than in the control group indicating that in PWS failure of peripheral release of CCK in response to food intake was not the explanation for the impaired satiety response.
Reconstructing the binding site of factor Xa in trypsin reveals ligand-induced structural plasticity.
In order to investigate issues of selectivity and specificity in protein-ligand interactions, we have undertaken the reconstruction of the binding pocket of human factor Xa in the structurally related rat trypsin by site-directed mutagenesis. Three sequential regions (the "99"-, the "175"- and the "190"- loops) were selected as representing the major structural differences between the ligand binding sites of the two enzymes. Wild-type rat trypsin and variants X99rT and X(99/175/190)rT were expressed in yeast, and analysed for their interaction with factor Xa and trypsin inhibitors. For most of the inhibitors studied, progressive loop replacement at the trypsin surface resulted in inhibitory profiles akin to factor Xa. Crystals of the variants were obtained in the presence of benzamidine (3), and could be soaked with the highly specific factor Xa inhibitor (1). Binding of the latter to X99rT results in a series of structural adaptations to the ligand, including the establishment of an "aromatic box" characteristic of factor Xa. In X(99/175/190)rT, introduction of the 175-loop results in a surprising re-orientation of the "intermediate helix", otherwise common to trypsin and factor Xa. The re-orientation is accompanied by an isomerisation of the Cys168-Cys182 disulphide bond, and burial of the critical Phe174 side-chain. In the presence of (1), a major re-organisation of the binding site takes place to yield a geometry identical to that of factor Xa. In all, binding of (1) to trypsin and its variants results in significant structural rearrangements, inducing a binding surface strongly reminiscent of factor Xa, against which the inhibitor was optimised. The structural data reveal a plasticity of the intermediate helix, which has been implicated in the functional cofactor dependency of many trypsin-like serine proteinases. This approach of grafting loops onto scaffolds of known related structures may serve to bridge the gap between structural genomics and drug design.