Salvage therapy for prostate cancer recurrence after radiation therapy

Radiotherapy has been successful in treating localized prostate cancer; however, a subset of patients will experience disease recurrence. Determination of the recurrence location must be made using pretreatment and posttreatment clinical variables, imaging, and postradiotherapy biopsy. Patients presumed to have local-only recurrence, optimal clinical risk factors, and an extended life expectancy may be considered for salvage local treatment. Current options include salvage surgery, cryoablation, and brachytherapy. Although they are associated with higher morbidity than primary therapy, salvage treatments can be effective and can still provide patients with a good oncologic and functional outcome. As these modalities continue to improve and patient selection is optimized, better results will evolve.     

Routine postoperative chest x-ray following laparoscopic nephrectomy.

PURPOSE: To determine whether a routine postoperative chest x-ray is required following uneventful laparoscopic nephrectomy to rule out pneumothorax. METHODS: From June 1999 to May 2003, 308 laparoscopic nephrectomy cases were performed by 5 different surgeons. This consisted of 121 radical nephrectomies, 106 donor nephrectomies, 29 simple nephrectomies, 29 partial nephrectomies, and 23 nephroureterectomies. Of the 308 procedures, 186 postoperative chest x-ray s were obtained in the recovery room: 183 routinely and 3 for known intraoperative diaphragmatic injuries. Routine chest x-rays were not obtained in 122 cases due to the individual surgeon's preference. Of these 122 patients, 15 underwent chest x-ray performed while hospitalized secondary to pulmonary issues or fever. RESULTS: Of the 308 cases, 4 pneumothoraces were identified on chest x-ray. Three were identified in the patients who had intraoperative identification of diaphragmatic injury. The fourth pneumothorax was identified in a patient who did not have a routine postoperative chest x-ray but did have a chest x-ray obtained due to postoperative shoulder pain. The pneumothorax in this patient resolved spontaneously. No incidental findings existed of pneumothorax in any patient who underwent routine postoperative chest x-ray. CONCLUSION: In our series, a pneumothorax was identified either intraoperatively or based on postoperative clinical findings. None of the 183 routine postoperative chest x-rays changed patient management. Routine postoperative chest x-ray is not necessary in uncomplicated laparoscopic nephrectomy.     

In vivo detection of single cells by MRI.

The use of high-relaxivity, intracellular contrast agents has enabled MRI monitoring of cell migration through and homing to various tissues, such as brain, spinal cord, heart, and muscle. Here it is shown that MRI can detect single cells in vivo, homing to tissue, following cell labeling and transplantation. Primary mouse hepatocytes were double-labeled with green fluorescent 1.63-microm iron oxide particles and red fluorescent endosomal labeling dye, and injected into the spleens of recipient mice. This is a common hepatocyte transplantation paradigm in rodents whereby hepatocytes migrate from the spleen to the liver as single cells. One month later the animals underwent in vivo MRI and punctuated, dark contrast regions were detected scattered through the livers. MRI of perfused, fixed samples and labeled hepatocyte phantoms in combination with histological evaluation confirmed the presence of dispersed single hepatocytes grafted into the livers. Appropriate controls were used to determine whether the observed contrast could have been due to dead cells or free particles, and the results confirmed that the contrast was due to disperse, single cells. Detecting single cells in vivo opens the door to a number of experiments, such as monitoring rare cellular events, assessing the kinetics of stem cell homing, and achieving early detection of metastases.     

Mathematical Models for Predicting the Epidemiologic and Economic Impact of Vaccination against Human Papillomavirus Infection and Disease

Infection with human papillomavirus (HPV) is the primary causeof cervical cancer, other anogenital cancers, genital warts,and recurrent respiratory papillomatosis. Clinical studies havedemonstrated that a prophylactic HPV vaccine can prevent infection,genital warts, and the precancerous lesions that lead to cervicalcancer. Given the absence of data on the long-term effectivenessof HPV vaccination, a number of mathematical models have beendeveloped to provide insight to policy makers by projectingthe long-term epidemiologic and economic consequences of vaccinationand evaluate alternative vaccination policies. This paper reviewsthe state of these models. Three types of HPV mathematical modelshave been reported in the literature: cohort, population dynamic,and hybrid. All have demonstrated that vaccination can significantlyreduce the incidence of cervical cancer in the long term. However,only the cohort and hybrid models have evaluated the cost-effectivenessof vaccination strategies for preventing cervical cancer. Thesemodels have generally shown that vaccinating females can becost-effective. None has accounted for the potential benefitsof vaccinating the population to reduce the burden of recurrentrespiratory papillomatosis and cancers of the vagina, vulva,anus, penis, and head/neck. Given that only the population dynamicmodel can account for both the direct and indirect (i.e., herdimmunity effects) benefits of vaccination in the population,future research should focus on further development of dynamicmodels by expanding the range of epidemiologic outcomes trackedand including the ability to assess the cost-effectiveness ofalternative vaccination policies. cost-benefit analysis • economics • papillomavirus, human • vaccines     

Logics and Logistics of Community Intervention Against Osteoporosis: An Evidence Basis

Under designations like small areas action research and intervention, directed ‘ground-up’ health promotion and prevention in the population form an important part of the ongoing medical systems development. There is recent evidence of the success of community intervention against cardiovascular disease. In osteoporosis, however, there is still a lack of conclusive data on both the logics and logistics of such an approach. Since 1988, a county health policy program has been formulated and implemented in Östergötland, Sweden, following the principles and guidelines of the WHO HFA 2000 declaration. Vadstena (n ? 7,600) was chosen for a local and generalizable osteoporosis prevention project mediated by the primary care organization by means of health promotion and education in the community. In the present report we emphasize that community intervention is an important new advancement of the medical systems, where the basic research questions include operational and management aspects as equally vital and measurable requisites and results as other performance and outcome variables. We found that a community intervention trial against osteoporosis is both motivated and feasible and in this report wish to provide evidence on these crucial issues of logics and logistics.     

Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGF-II immunoreactivity in postmenopausal women with osteoporosis.

Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12-24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo. INTRODUCTION: Recombinant teriparatide [human PTH(1-34)], a bone formation agent for the treatment of osteoporosis when given once daily subcutaneously, increases biochemical markers of bone turnover and activation frequency in histomorphometry studies. MATERIALS AND METHODS: We studied the mechanisms underlying this bone-forming action of teriparatide at the basic multicellular unit by the appearance of cement lines, a method used to directly classify surfaces as modeling or remodeling osteons, and by the immunolocalization of IGF-I and IGF-II. Transiliac bone biopsies were obtained from 55 postmenopausal women treated with teriparatide 20 or 40 microg or placebo for 12-24 months (median, 19.8 months) in the Fracture Prevention Trial. RESULTS: A dose-dependent relationship was observed in modeling and mixed remodeling/modeling trabecular hemiosteons. Trabecular and endosteal hemiosteon mean wall thicknesses were significantly higher in both teriparatide groups than in placebo. There was a dose-dependent relationship in IGF-II immunoreactive staining at all bone envelopes studied. The greater local IGF-II presence after treatment with teriparatide may play a key role in stimulating bone formation. CONCLUSIONS: Direct evidence is presented that 12-24 months of teriparatide treatment induced modeling bone formation at quiescent surfaces and resulted in greater bone formation at remodeling sites, relative to placebo.     

Synaptically evoked membrane potential oscillations induced by substance P in lamprey motor neurons.

Short-lasting application (10 min) of tachykinin neuropeptides evokes long-lasting (>24 h) modulation of N-methyl-D-aspartate (NMDA)-evoked locomotor network activity in the lamprey spinal cord. In this study, the net effects of the tachykinin substance P on the isolated spinal cord have been examined by recording from motor neurons in the absence of NMDA and ongoing network activity. Brief bath application of substance P (30 s to 2 min) induced irregular membrane potential oscillations in motor neurons. These oscillations consisted of depolarizing and hyperpolarizing phases and were associated with phasic ventral-root activity. The oscillations were blocked by the tachykinin antagonist spantide II. They were also blocked by tetrodotoxin (TTX), suggesting that they were not dependent on intrinsic membrane properties of the motor neurons but were synaptically mediated. Substance P could also have a direct effect, however, because a membrane potential depolarization persisted in the presence of TTX. Protein kinase agonists and antagonists were used to investigate the intracellular pathways through which substance P acted. The oscillations were blocked by the selective protein kinase C (PKC) antagonist chelerythrine. However, the TTX-resistant membrane potential depolarization was not significantly affected by blocking PKC. The protein kinase A and G antagonist H8 did not affect either the oscillations or the direct TTX-resistant membrane potential depolarization. The glutamate receptor antagonist kynurenic acid abolished the substance-P-evoked oscillations, suggesting that they were dependent on glutamate release. The oscillations were abolished or reduced by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxalene-2,3-dione but were only reduced by the NMDA receptor antagonist D-AP5. The oscillations were thus mediated by glutamatergic inputs with a greater dependence on non-NMDA receptors. Blocking glycinergic inputs with strychnine resulted in large depolarizing plateaus and bursts of spikes. The glutamatergic and glycinergic inputs underlying the oscillations are apparently evoked through direct and indirect excitatory effects on inhibitory and excitatory premotor interneurons. Substance P thus has a distributed excitatory effect in the spinal cord. While it can activate premotor networks, this activation alone is not able to evoke a coordinated behaviorally relevant motor output.     

How Cluster Headache is Explained as an Intracavernous Inflammatory Process Lesioning Sympathetic Fibers

SYNOPSIS
A large body of evidence points to an inflammatory process in the cavernous sinus and tributary veins as being primarily responsible for cluster headaches. The inflammation obliterates the venous outflow from the cavernous sinus on one side and injures the through-running sympathetic fibers to the eye, upper eye lid, forehead skin, and the intracranial internal carotid artery and its branches. The active period ends when the inflammation is suppressed and the sympathetic fibers partially or fully recover. Evidence is presented that the symptoms suggestive of an enhanced parasympathetic activity during attacks may alternatively be explained as local pain fiber activation or a stasis in the outflow from the cavernous sinus. Vasodilator agents like nitroglycerin induce an attack by enhancing the venous load on the cavernous sinus. Constriction of the proximal intracranial internal carotid artery, spontaneously induced by tressful pain activation of the perivascular sympathetic nerves, or by exogenous administration of serotonin 1 D-like receptor agonists or oxygen, terminates the venous load and thus the pain and associated symptoms.