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Three-year recurrence-free survival in a patient with recurrent medulloblastoma after resection, high-dose chemotherapy, and intrathecal Yttrium-90-labeled DOTA0-D-Phe1-Tyr3-octreotide radiopeptide brachytherapy.

BACKGROUND: Most medulloblastomas express high levels of somatostatin type 2 receptors (sst2). DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) specifically binds sst2 in the low nanomolar range. The cytotoxic effect is mediated by the chelated, beta-emitting, metallic radionuclide Yttrium 90 (90Y). The authors applied this innovative treatment option in a boy age 8 years who presented with a recurrent medulloblastoma of the cauda equina: a prognostically poor condition. Targeted radiotherapy was administered to treat minimal sst2-expressing tumor remnants, which persisted despite conventional and high-dose chemotherapy and intercurrent resection of the lesion. METHODS: A medulloblastoma arising from the floor of the fourth ventricle had been removed surgically; then, the patient was treated with standard adjuvant chemotherapy and craniospinal irradiation according to the prospective HIT '91 protocol. Complete remission was achieved for 20 months, when a drop metastasis of the cauda equina manifested with sensorimotor lumbosacral deficits and urinary incontinence. After four cycles of neoadjuvant chemotherapy (which consisted of combined ifosfamide, carboplatinum and etoposide), two cycles of high-dose chemotherapy and autologous stem cell transplantation were performed; in between, the responding residual tumor within the lumbosacral nerve fibers was microscopically removed. Thereafter, an Indium-111-DOTATOC test injection indicated sst2-expressing tumor remnants within the cauda equina. Consequently, 4 cycles of [90Y]-DOTATOC (4x562.5 megabecquerels) were injected directly into the cerebrospinal fluid in monthly intervals. RESULTS: The consolidating intrathecal brachytherapy using [90Y]-DOTATOC was tolerated well. A complete remission was achieved for a 3-year period. The only remaining deficit was urinary incontinence. CONCLUSIONS: Intrathecal administration of targeted radiopeptide brachytherapy in combination with conventional and high-dose chemotherapy and surgical removal represents a promising new option to treat recurrent medulloblastoma and should be explored further.

Antineoplastic Agents↗

The prevalence of recurrent spontaneous abortions, cancer, and congenital anomalies in the families of couples with recurrent spontaneous abortions or gestational trophoblastic tumors.

This study extends our previous work on the genetics of recurrent spontaneous abortion and of gestational trophoblastic tumors in an ethnically homogeneous population of Chinese in Taiwan by comparing the prevalence of recurrent spontaneous abortions, cancer, and congenital anomalies in the first-, second-, and third-degree relatives of the index couples to that of normally fertile couples from the same population. The rationale for this study was to provide another test for our hypothesis that genes linked to the major histocompatibility complex are responsible for the diseases in the index couples. If they are, these genes should segregate with a higher frequency in the relatives of the index couples than in the relatives of normally fertile couples and lead to a higher prevalence of these diseases in the extended families. Such a difference was found and adds support to our hypothesis that major histocompatibility complex-linked genes affect growth, development, and susceptibility to cancer.

Abortion, Spontaneous↗

Recurrent oral ulcerations associated with recurrent herpes labialis--two distinct entities?

We investigated the prevalence of recurrent aphthous ulcerations (RAU) and recurrent herpes labialis (RHL) in a young adult population. The study group consisted of 20,689 soldiers (aged 18-21 years, mean 19.8 +/- 1 years). There were 14,991 men and 5,698 women. Every patient was asked to complete a self-report health questionnaire which requested information about the occurrence of either RAU or RHL. Data were analyzed using the chi-square test, and the odds ratio was also determined. The prevalence of RAU and RHL was 6.2% and 5.4%, respectively. The prevalence among women was significantly higher (P<0.001), than among men for both RAU (7.1% and 5.8%, respectively) and RHL (6.8% and 4.9%, respectively). Among women, the chance of having RAU for those who were RHL positive was 6.88 greater than for those RHL negative. Among men, the chance of having RAU for those who were RHL positive was 12.37 greater than for those RHL negative. In women, the chance of having RHL for those who were RAU positive was 6.88 greater than for those who were RAU negative. In men, the chance of having RHL for those who were RAU positive was 12.37 greater than for those who were RAU negative. It is concluded that a similar underlying pathological process or unknown cofactor may be involved in both RAU and RHL.

Adolescent↗

Recurrent conditioning in the cat spinal cord. Differential effect of meprobamate on recurrent facilitation and inhibition.

The action of cumulative doses of meprobamate on antidromic conditioning has been studied in spinal cats. Recurrent facilitation is greatly reduced or completely abolished by total doses ranging from 210 to 400 mg./kg. The depth of recurrent inhibition is not affected in a consistent manner by meprobamate, but the duration of inhibition is markedly increased in all experiments. This differential action of meprobamate on facilitation and inhibition can be utilized to study conditioning effects consisting of combined inhibition and facilitation. If conditioning starts with an inhibitory phase, variable in duration, followed by facilitation, meprobamate depresses the facilitation and reveals an extended inhibitory curve. Facilitation, however, is not always accompanied by inhibition, since in some cases facilitation is depressed and no inhibition is uncovered. The results of these experiments are discussed in relation to the various types of conditioning that have been produced by antidromic stimulation.

Animals↗

Distribution of recurrent inhibition within a motor nucleus. II. Amount of recurrent inhibition in motoneurones to fast and slow units.

The maximal recurrent inhibition was studied by intracellular recording from 43 triceps surae motoneurones (tentatively type-identified by the biophysical properties of the neurones) and from 67 medial gastrocnemius motoneurones (type-identified by the muscle unit properties; fast fatiguing, FF; fatigue resistant, FR and slow, S). Maximal homonymous recurrent IPSP (RIPSP) and input resistance (RN) were measured at 'resting' membrane potential and close to firing threshold. The 'synaptic current' at the peak of the RIPSP was estimated (RIPSP/RN). At 'resting' membrane potential the RIPSPs increased in the order FF less than FR less than S (0.9, 1.4, and 2.5 mV, respectively). This order was preserved when the 'current' (RIPSP/RN) rather than voltage was considered, although the overall range was much reduced. When investigated close to firing threshold there were no significant differences in synaptic 'current'. This apparent paradox may be explained by systematic differences in firing threshold between motor unit types; it increased in the order S less than FR less than FF (4.6, 8.9 and 13.5 mV, respectively).

Animals↗

Comparison of warfarin versus aspirin for the prevention of recurrent stroke or death: subgroup analyses from the Warfarin-Aspirin Recurrent Stroke Study.

BACKGROUND AND PURPOSE: We performed a combination of prespecified and exploratory subgroup analyses to detect any treatment differences among various baseline subgroups in the Warfarin-Aspirin Recurrent Stroke Study (WARSS) cohort. METHODS: The WARSS compared the efficacy of adjusted-dose warfarin (INR 1.4-2.8) to aspirin (325 mg/day) for recurrent ischemic stroke or death within 2 years. The effect of warfarin and aspirin was compared among prespecified and exploratory subgroups with respect to sociodemographic and vascular risk factors, stroke subtype, arterial territory, and infarct topography. Hazard ratios and 95% confidence intervals comparing warfarin to aspirin were calculated using Cox proportional hazards models. Differences in hazard ratios were tested using interaction terms. RESULTS: No treatment differences between warfarin and aspirin were found across multiple prespecified subgroups. In a multivariate model, warfarin was associated with greater hazard among patients with moderate stroke severity (HR 1.63, 95% CI 1.005-2.64, p = 0.047) and a greater benefit among those with posterior circulation location without brainstem infarction (HR 0.54, 95% CI 0.33-0.88, p = 0.013). In post-hoc analyses of the cryptogenic subgroup, warfarin was associated with worse outcomes among patients with moderate stroke severity and better outcomes among those without baseline hypertension or with posterior circulation infarcts sparing the brainstem. CONCLUSIONS: In the WARSS, the majority of subgroup analyses showed no benefit of warfarin over aspirin. Warfarin benefit was limited to brainstem-sparing posterior circulation infarcts and select cryptogenic stroke subgroups. Pending future clinical trial evidence to the contrary, antiplatelets are recommended for survivors of noncardioembolic stroke.

Aged↗

Onychomycosis: review of recurrence rates, poor prognostic factors, and strategies to prevent disease recurrence.

Treatment of onychomycosis is associated with substantial disease reappearance rates. Identification of factors associated with therapeutic failure may help develop strategies to prevent recurrence of onychomycosis. Aspects of a patient's health and lifestyle, local factors involving the nail, therapeutic options, and environmental conditions are associated with poor therapeutic response. Strategies to reduce recurrence of disease involve the reduction of both relapse (delayed failure) and reinfection. The topical antifungal agent ciclopirox nail lacquer, may be a consideration for prophylaxis of this chronic disease.

Antifungal Agents↗

Recurrent Cushing's syndrome due to recurrent adrenocortical tumor--fragmentation or tumor in ectopic adrenal tissue?

A 33-yr-old woman was found to have Cushing's syndrome due to a left adrenal cortical tumor. The tumor and the surrounding adrenal gland were removed intact and in toto. Four years later, she noticed recurrent symptoms of Cushing's syndrome, and 6 yr postoperatively, an adrenal tumor was demonstrable on computed tomography. Fourteen years after the initial procedure, a left adrenal tumor, presumably arising in ectopic adrenal tissue, was removed with relief of her symptoms of Cushing's syndrome. The site and functional capacity of ectopic adrenal tissues are reviewed.

Adrenal Cortex Neoplasms↗

Recurrent chromosomal imbalances in nonsmall cell lung carcinoma: the association between 1q amplification and tumor recurrence.

BACKGROUND: Lung carcinoma is a leading cause of cancer deaths worldwide. To better understand this disease, the authors studied genetic alterations in nonsmall cell lung carcinoma (NSCLC) and the association between genetic changes and clinical features. METHODS: Genetic alterations in 30 patients with adenocarcinoma (AC) and 39 patients with squamous cell carcinoma (SCC) were analyzed by comparative genomic hybridization. The genetic changes in patients with AC and SCC were compared and the associations of these changes with clinical features were studied. RESULTS: A gain of 3q with a minimal amplified region at 3q25.3-qter was significantly higher in patients with SCC compared with patients with AC (72% vs. 27%; P < 0.001). A gain of 20q and loss of chromosome 9 were detected more frequently in patients with AC compared with patients with SCC (P < 0.05). Gains of 5p and 20q and loss of 5q were significantly correlated with an advanced stage of NSCLC (P < 0.05). Amplification of 1q was significantly associated with NSCLC recurrence (P = 0.04). CONCLUSIONS: The results of the current study suggested that different chromosomal aberrations may contribute to the types and pathologic stages of NSCLC.

Adenocarcinoma↗

Results of surgical treatment for recurrent hepatocellular carcinoma; comparison of outcome among patients with multicentric carcinogenesis, intrahepatic metastasis, and extrahepatic recurrence.

No consensus has been reached on the indications for and effectiveness of surgery for secondary intrahepatic hepatocellular carcinoma (HCC) and extrahepatic metastasis after macroscopically complete removal of primary HCC. Secondary intrahepatic HCCs, usually regarded as recurrence are classified into those arising as a result of multicentric carcinogenesis or intrahepatic metastases derived from the primary HCC. The present study was designed to evaluate the utility of surgical treatment in relation to the pathogenesis of the secondary HCC: classified as multicentric carcinogenesis (MC), intrahepatic metastasis (IM), and extrahepatic metastasis. Thirty patients underwent extirpation of secondary HCC: 22 patients had secondary HCCs in the remnant liver (MC group; n = 8; IM group, n = 14), 6 patients had extrahepatic metastases, and 2 patients had both intrahepatic and extrahepatic metastases. Survival rates after the re-resection in the 22 patients with the secondary intrahepatic HCCs were 94.7% at 1 year, and 50.2% at 3 years postoperatively, and the 8 patients with extrahepatic metastasis had survival rates of 62.5% at 1 year, 37.5% at 3 years, and at 5 years. The survival rates after re-resection in the MC group were 100% at 1 year and 80.0% at 3 years, whereas those in the IM group were 91.7% at 1 year, and 38.1% at 3 years. Surgery can be indicated not only in patients with localized intrahepatic secondary HCCs but also in those with extrahepatic metastasis. In particular, patients with secondary HCCs arising as a result of multicentric carcinogenesis are expected to have a good prognosis.

Adult↗

[Recurrent familial cardiac myxomas and lentiginosis. Second recurrence in a 41-year-old female patient].

The case of a 41-year-old woman with recurrent cardiac myxomas and widespread lentiginosis is reported. The diagnosis of a Carney complex was established 7 and 25 years, respectively, after first manifestation of the cardiac myxomas in both the patient and her brother. This peculiar hereditary disease is commonly associated with multiple neoplasms and an endocrine overactivity, requiring a thorough examination of the patients and their relatives to detect additional typical manifestations.

Adult↗

Increased sensitivity to stress and episode recurrence in spontaneous recurrence of methamphetamine psychosis.

Increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes may precipitate stress-related psychiatric disorders. The present study examines the relation between this increased sensitivity and vulnerability to subsequent spontaneous recurrences of methamphetamine (MAP) psychosis (i.e. flashbacks). Plasma monoamine metabolite levels were assayed in 18 subjects with flashbacks, of whom ten experienced a single flashback and eight experienced further subsequent flashbacks; in 21 subjects with a history of MAP psychosis who did not experience flashbacks; and 33 controls. A square-root transformation was applied to monoaminergic values, rendering the distribution normal. The subjects with flashbacks had undergone frightening stressful experiences during previous MAP use. The dominant factor triggering flashbacks was a mild fear of other people. During flashbacks, plasma noradrenaline levels markedly increased and 3-methoxytyramine levels, an indicator of dopamine release, were elevated. Among the 18 subjects with flashbacks, the ten with subsequent flashbacks had markedly increased noradrenaline levels during flashbacks, whereas the eight with a single flashback displayed small increases in noradrenaline levels as well as 3-methoxytyramine levels. Thus, a mild fear of other people may have elicited memories of MAP psychosis, related to frightening stressful experiences through increased sensitivity to stress associated with noradrenergic hyperactivity, involving increased dopamine release. Robust noradrenergic hyperreactivity to mild stress may predispose subjects to subsequent flashbacks.

Adult↗

A case with recurrent calf pain and swelling: recurrent spontaneous calf haematoma.

The differential diagnosis of unilateral calf swelling and pain includes deep venous thrombosis, haematoma, ruptured popliteal cyst, infection, lymph oedema, and sarcoma. It is important to distinguish between these entities, as the treatment of each is different. We present a case of recurrent calf swelling due to spontaneous calf haematoma diagnosed with ultrasound and MRI and subsequently treated conservatively.

Edema↗

Locoregional recurrence after doxorubicin-based chemotherapy and postmastectomy: Implications for breast cancer patients with early-stage disease and predictors for recurrence after postmastectomy radiation.

PURPOSE: To compare rates of locoregional recurrence (LRR) after mastectomy, doxorubicin-based chemotherapy, and radiation with those of patients receiving mastectomy and doxorubicin-based chemotherapy without radiation and to determine predictors of LRR after postmastectomy radiation. METHODS: Kaplan-Meier freedom-from-LRR rates were calculated for 470 patients treated with mastectomy, doxorubicin-based chemotherapy, and postmastectomy radiation in five single-institution clinical trials. The LRR rates in these patients were compared to previously reported rates in 1031 patients treated without radiation in the same trials. RESULTS: Median follow-up was 14 years. Irradiated patients had significantly less favorable prognostic factors for LRR than did unirradiated patients. Despite this, in all subsets of node-positive patients, postmastectomy radiation led to lower rates of LRR. This included patients with T1 or T2 tumors and one to three positive nodes (10-year LRR rates of 3% vs. 13%, p = 0.003). Multivariate analysis of LRR for patients with this stage of disease revealed that no radiation, close/positive margins, gross extracapsular extension, and dissection of <10 nodes predicted for increased LRR (hazard ratios 6.25, 4.61, 3.27, and 2.66, respectively). Significant predictors of LRR for patients treated with postmastectomy radiation were higher number and >or=20% positive nodes, larger tumor size, lymphovascular space invasion, and estrogen receptor (ER)-negative disease. Recursive partitioning analysis revealed ER-negative status to be the most powerful discriminator of LRR in irradiated patients. CONCLUSIONS: Postmastectomy radiation decreases LRR for patients with breast cancer, including those with Stage II breast cancer and one to three positive lymph nodes.

Adult↗

Factors for susceptibility to episode recurrence in spontaneous recurrence of methamphetamine psychosis.

The relation between increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes, and susceptibility to subsequent spontaneous recurrences of methamphetamine (MAP) psychosis (flashbacks) was examined. Plasma monoamine metabolite levels were assayed in 19 flashbackers, of whom 10 experienced a single flashback and 9 exhibited subsequent flashbacks, 18 nonflashbackers with a history of MAP psychosis, 9 subjects with persistent MAP psychosis, and 22 MAP user and 10 nonuser controls. All flashbackers had undergone frightening stressful experiences during previous MAP use. They exhibited flashbacks in response to mild psychosocial stressors. There was no significant difference in the number of stressful experiences and having mild psychosocial stressors between the two flashbacker subgroups. Plasma norepinephrine (NE) levels increased with a small increase in plasma levels of 3-methoxytyramine (3-MT), an index of dopamine release, during flashbacks in the 19 flashbackers. Of the 19 flashbackers, the 9 with subsequent episodes had markedly increased NE levels and slightly increased 3-MT levels during flashbacks, while the 10 with a single episode displayed small increases in NE and 3-MT levels during flashbacks. The 9 flashbackers with subsequent episodes had a longer duration of imprisonment than the 10 flashbackers with a single episode. Thus, robust noradrenergic hyperactivity with slightly increased DA release in response to mild stress may predict subsequent flashbacks. Long-term exposure to distressing situations appears to contribute to susceptibility to subsequent flashbacks.

Dopamine↗

Colonic IgA producing cells and macrophages are reduced in recurrent and non-recurrent Clostridium difficile associated diarrhoea.

BACKGROUND: In Clostridium difficile associated diarrhoea (CDAD), histological changes in the colonic mucosa range from minimal inflammation to pseudomembranous colitis (PMC). The disease also recurs in a considerable proportion of patients. AIM: To investigate mucosal immune system cells in colonic biopsies of patients with CDAD. METHODS: Colonic biopsies were obtained from 12 control patients with diarrhoea, six patients with CDAD and minimal inflammation, and 10 patients with CDAD with pseudomembranous colitis (samples obtained from areas with and without inflammatory exudate). Immunohistochemical studies were performed using antibodies to T cells (CD3), macrophages (CD68), B/plasma cells (CD79alpha), and to IgA, IgM, and IgG. Labelled cells in lamina propria were quantified. RESULTS: In contrast to T cells, there were significant reductions in B/plasma cell and macrophage counts in all biopsies from patients with CDAD compared with controls (p<0.001). Studies using anti-immunoglobulin antibodies showed significant reductions in IgA producing cells in CDAD biopsies (p<0.05), with the greatest reduction in samples from patients with PMC. In contrast, there was a significant increase (p<0.05) in IgG producing cells in CDAD biopsies. Only patients with PMC relapsed. In these patients, B/plasma cell and IgA producing cell counts (in biopsies with and without inflammatory exudates) were significantly lower (p<0.01) in mucosal samples from those who subsequently relapsed (five) than those who did not. CONCLUSIONS: A selective reduction in mucosal IgA producing cells and macrophages is associated with colonic disease in C difficile infected patients. Severe reduction in colonic IgA producing cells may predispose to recurrence of CDAD.

Adolescent↗

VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial.

BACKGROUND: Plasma triglyceride concentration has been an inconsistent independent risk factor for coronary heart disease, perhaps because of the metabolic heterogeneity among VLDL particles, the main carriers of triglycerides in plasma. METHODS AND RESULTS: We conducted a prospective, nested case-control study in the Cholesterol and Recurrent Events (CARE) trial, a randomized placebo-controlled trial of pravastatin in 4159 patients with myocardial infarction and average LDL concentrations at baseline (115 to 174 mg/dL, mean 139 mg/dL). Baseline concentrations of VLDL-apolipoprotein (apo) B (the VLDL particle concentration), VLDL lipids, and apoCIII and apoE in VLDL+LDL and in HDL were compared in patients who had either a myocardial infarction or coronary death (cases, n=418) with those in patients who did not have a cardiovascular event (control subjects, n=370) in 5 years of follow-up. VLDL-cholesterol, VLDL-triglyceride, VLDL-apoB, apoCIII and apoE in VLDL+LDL and apoE in HDL were all interrelated, and each was a univariate predictor of subsequent coronary events. The significant independent predictors were VLDL-apoB (relative risk [RR] 3.2 for highest to lowest quintiles, P:=0.04), apoCIII in VLDL+LDL (RR 2.3, P:=0.04), and apoE in HDL (RR 1.8, P:=0.02). Plasma triglycerides, a univariate predictor of coronary events (RR 1.6, P:=0.03), was not related to coronary events (RR 1.3, P:=0.6) when apoCIII in VLDL+LDL was included in the model, whereas apoCIII remained significant. Adjustment for LDL- and HDL-cholesterol did not affect these results. CONCLUSIONS: The plasma concentrations of VLDL particles and apoCIII in VLDL and LDL are more specific measures of coronary heart disease risk than plasma triglycerides perhaps because their known metabolic properties link them more closely to atherosclerosis.

Apolipoprotein C-III↗