Diagnosis and treatment of HIV-related Kaposi's sarcoma

A 42-year-old heterosexual man presented with bluish-purple spots on his skin and in his mouth cavity that had been present for a few months; a 48-year-old homosexual man had painful lymphadenopathy in the groins and left axilla. Both men appeared to have a Kaposi's sarcoma and to be HIV-positive. During highly active antiretroviral therapy (HAART) and radiotherapy or chemotherapy, both the AIDS parameters and the skin lesions improved. Kaposi's sarcoma is AIDS-defining in HIV-seropositive patients. Human herpesvirus-8 infection seems to play a role in the development of Kaposi's sarcoma. The incidence of Kaposi's sarcoma has declined since the introduction of HAART. Nowadays, Kaposi's sarcoma is frequently the presenting symptom of HIV-seropositivity. Patients present with purple cutaneous lesions and/or generalised lymphadenopathy. Visceral lesions are associated with a shorter median survival. The treatment of Kaposi's sarcoma is palliative, whereas immune restitution can lead to regression of the sarcoma.     

Imaging pain modulation by subanesthetic S-(+)-ketamine

Little is known about the effects of low-dose S-(+)-ketamine on the cerebral processing of pain. We investigated the effects of subanesthetic IV S-(+)-ketamine doses on the perception of experimental painful heat stimuli. Healthy volunteers were evaluated with functional magnetic resonance imaging (fMRI) while receiving the painful stimuli in conjunction with placebo and increasing doses (0.05, 0.1, 0.15 mg x kg(-1) x h(-1)) of ketamine infusion. Vital variables were monitored and all subjects rated pain intensity and unpleasantness on a numerical rating scale. Alterations in consciousness were measured using a psycho-behavioral questionnaire. Pain unpleasantness declined as ketamine dosage was increased (55.1% decrease, placebo versus 0.15 mg x kg(-1) x h(-1) ketamine). Pain intensity ratings also decreased with increasing ketamine dosage but to a lesser extent (23.1% decrease). During placebo administration, a typical pain activation network (thalamus, insula, cingulate, and prefrontal cortex) was found, whereas decreased pain perception with ketamine was associated with a dose-dependent reduction of pain-induced cerebral activations. Analysis of the dose-dependent ketamine effects on pain processing showed a decreasing activation of the secondary somatosensory cortex (S2), insula and anterior cingulate cortex. This part of the anterior cingulate cortex (midcingulate cortex) has been linked with the affective pain component that underlines the potency of ketamine in modulating affective pain processing.     

Das gewebliche Verhalten des ovalen Fensters und der Cysterna perilymphatica nach typischer Vestibulotomie beim Kaninchen

Zusammenfassung Wie sich nach der Vestibulotomie bei vier Kaninchen und dem Verschluß des ovalen Fensters durch ein Transplantat aus der Conjunctiva ergibt, blieb letzteres frei von entzündlichen Reaktionen, es ist auch mit dem Fensterrahmen stets einwandfrei verwachsen. Die Überhäutung durch die Mittelohrschleimhaut wie das Endothel des Labyrinthes erfolgte vollständig. Im Bereich des ovalen Fensters bildete sich neuer Knochen, bei einem Fall annähernd in der Form des Steigbügels, in zwei Fällen in größerer Ausdehnung, hineinreichend in die Paukenhöhle wie in die Cysterna perilymphatica. In zwei Fällen war bereits am 28. Tag die Knochenneubildung vorhanden. Die Cysterne blieb nur in einem Fall frei, in einem anderen bildete sich ein Herd von neuem Knochen an der kranialen Wand. Obgleich sich diese Beobachtungen vom Kaninchen nicht ohne weiteres auf den Menschen übertragen lassen, verdienen sie immerhin im Hinblick auf die Stapesplastiken mit Gewebsinterposition Beachtung.Mit 3 Textabbildungen     

Thymidylate Synthase as a Prognostic Biomarker for Locally Advanced Rectal Cancer after multimodal Treatment

Purpose

For years, 5-fluorouracil (5-FU) has been the backbone of radiochemotherapy (RCT) of locally advanced rectal cancer. Its main target, thymidylate synthase (TS), is speculated to be an important biomarker for response prediction and long-term prognosis. In this study, we analyzed TS expression in the rectal cancer tissue of 208 patients to evaluate its predictive/prognostic potential.

Methods

All patients included were diagnosed with locally advanced adenocarcinoma of the rectum (UICC II and III) and were treated within randomized clinical trials of the German Rectal Cancer Study Group. Preoperative RCT (50.4 Gy and concomitant either 5-FU or 5-FU and oxaliplatin) was administered in 167 patients followed by surgical resection with total mesorectal excision (TME). Another 41 patients received postoperative RCT. TS levels and further clinicopathological parameters were assessed in univariate and multivariate analyses. Additionally, a TS gene polymorphism was analyzed with respect to the intratumoral protein levels.

Results

Low TS expression in pretreatment biopsies correlated with impaired patient survival (p = 0.015). Analysis of a 28-bp repeat revealed a correlation between the *3/*3 genotype and high TS expression in pretherapeutic biopsies. In this study, a correlation of TS expression and grade of RCT-induced tumor regression was not found. Histopathological examination confirmed a complete tumor remission in 16 patients (9.6%). Analyses of the resection specimen indicated an unfavorable prognosis for patients with low intratumoral TS expression in case of detected lymph node metastases (p = 0.04).

Conclusions

TS can serve as a prognostic biomarker indicating an unfavorable prognosis for patients with low TS expression.     

The effects of a lifestyle physical activity counseling program with feedback of a pedometer during pulmonary rehabilitation in patients with COPD: a pilot study

OBJECTIVE: To study the effects of a lifestyle physical activity counseling program with feedback of a pedometer during pulmonary rehabilitation. METHODS: Twenty-one chronic obstructive pulmonary disease (COPD) patients were randomized to an experimental group that followed a regular rehabilitation program plus the counseling intervention or to a control group that only followed rehabilitation. The primary outcome was daily physical activity assessed by pedometers. Secondary outcomes were physical fitness, health-related quality of life, activities of daily living, depression and self-efficacy. RESULTS: The experimental group showed an increase of 1,430 steps/day (+69% from baseline), whereas the control group showed an increase of 455 steps/day (+19%) (p = 0.11 for group x time interaction). The secondary outcomes showed no differences. CONCLUSION AND PRACTICE IMPLICATIONS: This study showed that the use of the pedometer, in combination with exercise counseling and the stimulation of lifestyle physical activity, is a feasible addition to pulmonary rehabilitation which may improve outcome and maintenance of rehabilitation results.     

Evidence from increased anticipation of predictive saccades for a dysfunction of fronto-striatal circuits in obsessive-compulsive disorder

In obsessive-compulsive disorder (OCD), a dysfunction of neuronal circuits involving prefrontal areas and the basal ganglia is discussed that implies specific oculomotor deficits. Performance during reflexive and predictive saccades, antisaccades and predictive smooth pursuit was compared between patients with OCD (n=22), patients with schizophrenia (n=21) and healthy subjects (n=24). Eye movements were recorded by infrared reflection oculography. In both patient groups, higher frequencies of anticipatory saccades with reduced amplitudes in the predictive saccade task were observed. Additionally, reduced smooth pursuit eye velocity and increased frequencies of saccadic intrusions during smooth pursuit as well as increased error rates in the antisaccade task were demonstrated for patients suffering from schizophrenia. Patients with OCD and schizophrenia revealed different patterns of oculomotor impairment: whereas increased anticipation of predictive saccades provides evidence for a dysfunction of the circuit between the frontal eye field and the basal ganglia in both groups, results from the antisaccade task imply additional deficits involving the dorsolateral prefrontal cortex in schizophrenic patients. Furthermore, the cortical network for smooth pursuit (especially the frontal eye field) is also assumed to be disturbed in schizophrenia.     

Metastatic recurrence after complete resection of colorectal liver metastases: impact of surgery and chemotherapy on survival

Purpose

Surgery is the standard of care for resectable colorectal liver metastases (CRC-LM). Unfortunately, 60 % of patients develop secondary metastatic recurrence (SMR) after R0-resection of CRC-LM. We investigated the impact of surgical re-intervention and chemotherapy (Ctx) on survival in a consecutive series of patients with SMR.

Methods

From 01/2001 to 11/2011, 104 out of 178 consecutive patients with R0-resection of CRC-LM developed SMR and were evaluated. The impact of surgical and Ctx re-interventions on recurrence free (RFS) and cancer-specific survival (CSS) was analyzed. Median follow-up was 28.0 (95 %CI: 19.4–37.4) months.

Results

SMR occurred in 81 patients at a single site (49× liver, 18× lung, 14× other) and in 23 patients at multiple sites. Forty-two patients were scheduled for primary surgery. Fifty-three patients were classified as non-resectable and treated with median 5.0 [IQR, 3.0–10.0] cycles of Ctx, combined with an EGFR/VEGF-antibody in 27 patients. Nine patients received best supportive care only. R0/R1 resection could be achieved in 35 patients primarily and even in 8 patients secondarily after Ctx. Surgical morbidity and mortality were 16 and 0 %, respectively. The 5-year RFS rates for patients with R0 versus R1-resection were 22 and 24 % (p?=?0.948). The 5-year CSS rate for R0/R1-resected patients was 38 % versus 10 % for those patients treated by Ctx alone (p?<?0.001).

Conclusion

In SMR, surgical re-intervention is feasible and safe in a remarkable number of patients and offers significantly longer CSS compared to patients without resection.