Iron deficiency during first-line chemotherapy in metastatic cancers: a prospective epidemiological study.

PURPOSE: Anemia is common in oncology and negatively impacts quality of life. However, there is lack of knowledge about iron deficiency (ID) epidemiology. The aim of this study was to prospectively assess iron status in patients with locally advanced or metastatic cancer beginning chemotherapy. METHODS: In this prospective, multicenter cohort study, anemia and ID were evaluated in patients with locally advanced or metastatic solid tumors and lymphoma before starting chemotherapy. Blood samples were collected at inclusion (W0), 6 weeks (W6), and 12 weeks (W12). Prevalence was evaluated in the general population, according to tumor location and was correlated with tumor response. RESULTS: One hundred twenty-nine patients were enrolled between 2013 and 2015; 119 had solid tumors and 10 lymphomas. At W0, there were no significant difference between locations with a prevalence around 50-60% (range 47.2-70.4%) and only a trend for colorectal cancer (70.4%, P = 0.069) due to a higher prevalence of absolute ID (18.5%). Prevalence of ID+ decreased between W0 and W6 and remained stable until W12 due to the proportion of patients with ID and without anemia. However, anemia prevalence increased during W0 and W6 and remained stable to W6 from W12 due to patients with anemia but without ID. A significant correlation between tumor response and ID prevalence was found (P = 0.036). CONCLUSIONS: We confirm the high prevalence of ID and anemia in cancer patients. ID status is correlated to tumor response providing a strong rationale for iron monitoring during cancer management.

Sporadic Retroperitoneal Hemangioblastoma: Report of a Case and Review of the Literature.

We report a case of sporadic isolated hemangioblastoma arising from the retroperitoneum and provide a review of the scarce literature regarding this very rare tumor. Furthermore, we thoroughly describe the pathologic features and the broad differential diagnosis that should always be included in the study of any retroperitoneal soft tissue mass to arrive at the final diagnosis.

Treatment of myasthenia gravis by immunoadsorption of plasma.

We treated 16 patients with moderately severe to severe generalized myasthenia gravis (MG) by immunoadsorption (perfusion through a resin that adsorbs proteins) of 2,500 ml plasma on each of four alternate days. Fourteen patients who completed treatment all had significant improvement in strength (6 excellent, 6 good, and 2 fair), which began a mean of 42 hours after the first immunoadsorption, reached a maximum 4 days after the fourth immunoadsorption (mean, 250% of baseline strength), and returned to baseline over a mean of 2 months. Thirty-seven grams of plasma proteins were removed during each immunoadsorption, which required no replacement, compared with 175 grams during plasma exchange, which requires replacement with albumin. Serum or plasma concentration of all proteins fell, more so for most of the larger proteins than for the smaller ones: acetylcholine receptor antibody (AChR Ab) fell to a mean of 23% of original level, fibrinogen to 26%, C4 to 29%, IgM to 33%, IgG to 35%, CH50 to 41%, C3 to 42%, IgA to 54%, and albumin to 76%. All proteins, including AChR Ab, returned to their original levels within 1 to 3 weeks after the last immunoadsorption, while improvement in strength lasted a mean of 6 weeks longer. One seronegative patient had excellent improvement lasting more than a month. Activated complement C5a and white blood cell count rose during each immunoadsorption, while activated complement C3a fell, and each returned to its original level within hours. Eight patients had transient symptomatic hypotension attributable to withdrawal of blood more rapidly than it was returned; this hypotension was prevented or ameliorated by intravenous saline.(ABSTRACT TRUNCATED AT 250 WORDS)

Sinusitis caused by Legionella pneumophila in a patient with the acquired immune deficiency syndrome.

A patient with the acquired immune deficiency syndrome and Legionella pneumophila infection of the maxillary sinus is described. The organism was identified by direct immunofluorescence staining of sinus tissue. Because the Legionella species are intracellular pathogens, it is not surprising that this patient with a cellular immune defect was infected. However, no other site of Legionella infection was found. This appears to be the first reported case of upper respiratory tract infection by a Legionella species.

Reduced prostacyclin to thromboxane A2 ratio is correlated with central apneas in preterm infants.

Prostacyclin has a vasodilating effect on pulmonary vessels, whereas thromboxane A2 results in vasoconstriction. This study was designed to test the hypothesis that recurrent central apneas in preterm infants are correlated with a reduced prostacyclin to thromboxane A2 ratio. Twelve preterm infants with clinical events of apneas were matched with 12 control infants. Urinary concentration of 2,3-dinor-6-keto-PGF1alpha and 2,3-dinor-TxB2 was determined, and the ratio correlated with the number of central apneas (>20s) measured in overnight polygraphy. The number of central apneas >20s/12h was 97.4 (SE 7.8) in the study group, and 47.3 (SE 6.6) in the control group (p = 0.001). There was a significant correlation between the number of central apneas and the 2,3-dinor-6-keto-PGF1alpha/2,3-dinor-TxB2-ratio in all infants combined (r = -0.72, p < 0.0001) as well as in the two subject groups. Central apneas in premature infants are correlated with an decreased prostacyclin to thromboxane A2 ratio. The underlying pathomechanism may be increased intrapulmonary shunts with reflexive central apneas due to reduced pulmonary oxygenation.

Neonatal urinary prostanoid excretion.

Urinary excretion of prostanoids prostaglandin E2 (PGE2), PGE-M (7alpha-hydroxy-5,11-diketo-2,3,4,5,20-penta-19-carboxyprostano ic acid), 6-keto-PGF1alpha, 2,3-dinor-6-keto-PGF1alpha, thromboxane B2 (TxB2) 2,3-dinor-TxB2 and 11-dehydro-TxB2 was determined by gas chromatography/mass spectrometry in preterm and term infants to show that there is an age-dependent excretion rate of the above prostanoids in infants this young. Group I included premature children with normal postnatal development, Groups II and III included term children who were admitted in the neonatal period for observation because of feeding problems but who were subsequently found to be completely healthy. We present normal data of three primary prostanoids and four prostanoid metabolites. In Group I, excretion rates of 2,3-dinor-TxB2 were significantly lower than in Group II (P = 0.04) and in Group III (P = 0.05). Furthermore, the excretion rate of 11-dehydro-TxB2 in group I was significantly lower than in Group II (P = 0.05). We found no significant age-dependent differences between the three groups in excretion rates of PGE2, PGE-M, 6-keto-PGF1alpha, 2,3-dinor-6-keto-PGF1alpha, and TxB2.

Cheyne-Stokes respiration as an additional risk factor for pulmonary hypertension in a boy with trisomy 21 and atrioventricular septal defect.

Central ventilation disorders(1) and airway obstruction(2) with chronic hypoxemia are causally related to cor pulmonale. Pulmonary vascular resistance is often reversible, and hypoxic pulmonary hypertension often responds to treatment with supplemental oxygen. Oxygen therapy during sleep may be useful as a temporary palliative treatment in children with obstructive sleep apnea syndrome (3) and Cheyne-Stokes respiration (CSR) in congestive heart failure(4). This type of sleep-related breathing disorder is characterized by periodic crescendo-decrescendo alterations in tidal volume. Proposed mechanism include an increased central nervous system sensitivity to changes in arterial PCO2 and PO2, a decrease in total body stores of CO2 and O2 with resulting instability in arterial blood gas tensions in response to changes in ventilation, and an increased circulatory time. Clinical features of obstructive and central sleep-related breathing disorders include daytime somnolence, unusual breathing patterns, failure to thrive, and cyanosis masquerading as cyanotic congenital heart disease(2). Down syndrome is often associated with cardiac malformations, left to right shunt, and the development of pulmonary hypertension(5). However, this may be exacerbated by sleep-related breathing disorders, as illustrated in the following case report.

The use of fluconazole in the management of Candida peritonitis in patients on peritoneal dialysis.

In patients receiving peritoneal dialysis, fungal peritonitis is generally impossible to eradicate with previously available therapy in the absence of catheter removal. Corbella et al. described a patient with fungal peritonitis treated with fluconazole without catheter removal. We studied this drug's effectiveness in the treatment of 5 patients with peritonitis secondary to Candida species. Patients received a loading dose of 200-400 mg fluconazole, followed by 50-200 mg fluconazole daily. Patients improved initially after therapy with fluconazole. Abdominal pain and fever abated, dialysis returns cleared, cell counts decreased, and, in four cases, cultures were sterilized. Dialysate fluconazole levels were adequate. However, despite maintenance of fluconazole therapy, all patients had recurrent peritonitis within 1 month. Complete cure did not occur unless the Tenckhoff catheter was removed. When the catheter was removed, tip cultures grew pure Candida species, and microscopic examination of catheter sections revealed abundant yeast. Although there may be continued isolated reports of successful eradication of fungal peritonitis without catheter removal, we conclude that in the vast majority of cases catheter removal is required.

Four-year-old girl with Goldenhar-sequence and severe obstructive sleep apnea, symptoms, diagnosis and therapy.

Recently sleep related breathing disorders in children have received considerable attention. Unfortunately, cardiorespiratory polygraphy is expensive and time-consuming, and up until now today only a few pediatric hospitals have complete facilities for all-night cardiorespiratory polygraphy. Nevertheless, the prevalence of sleep related breathing disorders in children is higher than has previously been thought. To show the importance of proper diagnosis of sleep related breathing disorders, we report a case of a 4-year-old girl with severe obstructive sleep apnea caused by Goldenhar-sequence (facio-auriculo-vertebral dysplasia). Despite some treatment efforts to correct the aplastic right mandible, the symptoms of obstructive sleep apnea were not immediately recognized and remained untreated. Untreated obstructive sleep apnea led to growth and mental retardation. After polygraphic confirmation of obstructive sleep apnea and appropriate interdisciplinary treatment, the 4-year-old girl made rapid advances in growth and mental development.

A symptomatic de novo pheochromocytoma 23 years after liver transplantation: a case report and review of the literature.

We report a case of subacute onset of headaches and tremors with a newly discovered adrenal pheochromocytoma 23 years after an orthotopic liver transplantation and provide a review of the scarce literature regarding endocrine malignancies in liver transplant recipients. We describe the clinical presentation, diagnostic work-up, and management. This is the second case report in the literature of a de novo pheochromocytoma after solid organ transplantation. It shows that new-onset common symptoms in transplant recipients are always challenging and deserve a very thorough work-up until the cause of the symptoms is elucidated. A broad differential diagnosis should always be included in the study of any abnormalities in this patient population.

Intra-articular fibroma of tendon sheath of the shoulder joint: synovial fibroma.

The case of a 30-year-old woman with multiple loose bodies in the shoulder joint is presented. The patient complained of discomfort of her right shoulder. Conventional radiographs failed to reveal any abnormality of the shoulder. On MRI numerous loose bodies were detected that resembled synovial chondromatosis. Histologically, the loose bodies were composed of a benign fibroblastic lesion with diagnostic features of fibroma of tendon sheath, each surfaced by synoviocytes. The clinicopathologic features of intra-articular fibroma of tendon sheath are reviewed. We propose using the term "synovial fibroma" for tumors with histopathologic features of fibroma of tendon sheath arising in the synovium of joints.

Central apnoea and endogenous prostaglandins in neonates.

AIM: Central apnoeas without an identifiable precipitating cause frequently occur in the neonatal period. Serious apnoeas should be treated with ventilation-enhancing methylxanthines. Drugs such as opioids or prostaglandins (PGE2) are known to induce apnoea. PGE2 is an endogenous hormone that plays an important role in the regulation of neural activity and a relationship between PGE2 and central apnoeas has been postulated. METHODS: In order to test the hypothesis that the incidence of central apnoeas in preterm infants is related to endogenous PGE concentration, we measured the urinary concentration of PGE2 and PGE-M and determined the number of central apnoeas >10 s/12 h in overnight polygraphy in 18 preterm infants with apnoeas, bradycardias and desaturations, and 18 normal controls. RESULTS: We found 80.6 (SE 6.9) central apnoeas in the study group, and 52.9 (SE 4.1) in the control group (p = 0.002). Urinary PGE2 concentration was 25.9 (SE 6.1) ng/h/1.73 m2 in the control, 31.2 (SE 15.8) ng/h/1.73 m2 in the study group (p = n.s.), PGE-M concentration was 486 (SE 35) ng/h/1.73 m2 in the control and 1132 (SE 131) ng/h/1.73 m2 in the study group (p < 0.0001). There was a significant correlation between the number of central apnoeas and the PGE-M concentration in the study group (r = 0.68, p < 0.0001). CONCLUSION: Our results suggest a relationship between PGE and the respiratory system and open potential therapeutic options for the treatment of central apnoeas in neonates.

[Obstructive sleep apnea in the child: an interdisciplinary treatment concept with special reference to craniofacial changes]. / Obstruktive schlafbezogene Atmungsstörungen beim Kind: Ein interdisziplinäres Behandlungskonzept unter besonderer Berücksichtigung kraniofazialer Veränderungen.

Diagnosis and therapy of obstructive sleep-related breathing disturbances SRBD in adults may not be applied without hesitation to children. SRBD in newborn and infants are often due to craniofacial disturbances (Pierre Robin syndrome, Goldenhars syndrome etc.), obesity is of minor importance. More than 30 infants with SRBD and craniofacial changes have been diagnosed and successfully treated over a 2-year period. Conservative therapy starts immediately after birth. The first step in newborn with Pierre Robin syndrome, for instance, is prone position for protrusion of tongue and mandible and mandibular growth stimulation. Intermediate nightly nasopharyngeal tubes are an alternative to nCPAP-/BiPAP treatment. Conventional orthopaedic/orthodontic treatment should not be neglected, even if it takes years to become effective. Surgical therapies are able to support, sometimes to replace or at least to shorten conservative methods. In rare cases when prone position in combination with palatal plates in cases of Robin syndrome, for instance, are not fully effective, mandibular extension is indicated. Aplasia or defects demand adequate surgical reconstruction, even if this does not necessarily mean abolishment of SRBD. In contrast to adults adenotonsillectomy is highly effective in infants and does not only reduce SRBD, but also improves nasal breathing and thus positively influences facial growth. A relatively new method is gradual mandibular distraction osteogenesis according to Ilizarov, which also enhances soft tissue growth. Maxillary and mandibular advancement osteotomies should not be considered before the termination of facial growth. Thanks to this refined treatment concept we were able to avoid tracheotomies in children during the past few years.

Cholera toxin enhances adenylate cyclase-dependent transport in toad urinary bladder.

Cholera toxin (CT) irreversibly ADP-ribosylates and activates the nucleotide-stimulatory (Ns) subunit of adenylate cyclase in many tissues, thereby eliciting cyclase-dependent functions. Although earlier studies performed at room temperature could not demonstrate CT-stimulated water transport in toad urinary bladder, subsequent work in other tissues has emphasized the need for incubation at 35-37 degrees C to effect ribosylation and the subsequent physiological effects. We found that incubating tissues with amphibian culture media, rather than Ringer solution, maintained tissue viability at this higher temperature and permitted prolonged incubation with CT. At 37 degrees C, in the presence of 0.1 mM phosphodiesterase inhibitor (1-methyl-3-isobutylxanthine, MIX), 0.2-200 nM mucosal CT caused a dose-dependent but submaximal enhancement of water flux and urea transport. Elimination of MIX from the bath diminished subsequent CT-induced stimulation, supporting a role for adenosine 3',5'-cyclic monophosphate (cAMP) as mediator of the CT effect. The increased water flow was stable for greater than 1 h after removal of CT from the bath, consistent with irreversible stimulation of the cyclase. Mucosal CT stimulated transport to a greater degree than serosal CT, paralleling the pattern seen in the intestine, which is compatible with passage of the toxin's a subunit across the cell to the serosal membrane cyclase. Exposure of the tissue's mucosal surface to GM1 ganglioside, (the natural receptor for the CT b subunit) yielded maximal stimulation of water flow and near-maximal urea transport, presumably by increasing CT's binding to the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Alternative base pairing between 5'- and 3'-terminal sequences of small subunit RNA may provide the basis of a conformational switch of the small ribosomal subunit.

The compiled sequences of small subunit ribosomal RNAs have been screened for base complementary between 5'- and 3'-terminal regions. Highly conserved complementary sequences are found which allow formation of a helix between the two ends of 5 or 6 base pairs. This helix is composed of sequences from the loop region of the first 5'-terminal stem and from sequences immediately distal to the last stem (the Me2A-stem) of the 3' terminus and therefore allows a coaxial stacking with either of these two flanking stems. Formation of the 5'/3'-helical arrangement is, however, only possible at the cost of dissolving the 'pseudo-knot' helix between the 5'-terminal region and the internal region of small subunit RNA. It is postulated that the mutually exclusive conformational states are in dynamic equilibrium and that they correlate with distinct functional states of the small ribosomal subunit. The 'pseudo-knot' containing conformation with the 3'-terminal sequences more exposed is likely to represent the initiating state, whereas the 5'/3' terminal paired 'closed' conformation may represent the elongating state in which interaction with fortuitous ribosomal binding sequences of mRNAs is avoided.

Different patterns of sighs in neonates and young infants.

To examine the prevalence and clinical assessment of sighs in neonates, we observed three different patterns of sighs: (A) sighs in the absence of apneic pause; (B) sighs with instantly following apneic pause >2 s, and (C) sighs with apneic pause >2 s following 1-3 normal breaths. We investigated preterm and term infants with 12 h nocturnal polygraphic recording. Sighs were more frequent in preterm than in term infants and more so during REM sleep than non-REM sleep. The part of sighs B of total number of sighs increased with gestational age. During REM sleep sighs without apnea were predominant, whereas apnea-associated sighs were mainly found during non-REM sleep.

Hypertrophic phenotype of cardiac calcium/calmodulin-dependent protein kinase II is reversed by angiotensin converting enzyme inhibition.

Calcium-dependent mechanisms and the renin angiotensin system (RAS) are critically involved in the hypertrophic growth of the myocardium. The calcium/calmodulin-dependent protein kinase II (CaMKII) is a ubiquitous mediator in calcium signaling and modulates calcium handling and growth mechanisms in cardiomyocytes. Here we present data on expression of cardiac isoforms of CaMKIIdelta, the dominant form in the myocardium, in compensatory hypertrophy of stroke-prone spontaneously hypertensive rats (SHRSP) compared to the normotensive Wistar-Kyoto (WKY) control strain. Cardiac hypertrophy in SHRSP was documented by an increased heart weight/body weight ratio (HW/BW) of 31% (p < 0.05) and a more than six-fold elevated atrial natriuretic factor (ANF) transcript level (p < 0.05). Compensatory hypertrophic growth in SHRSP produced a specific phenotype of CaMKIIdelta isoforms characterized by increased transcript levels of the embryonic/neonatal isoform delta4 (48%, p < 0.05) and the isoform delta9 (31%, p < 0.05) with no changes in delta2 and delta3. Inhibition of angiotensin converting enzyme (ACE) by cilazapril completely regressed myocardial hypertrophy, normalized ANF transcript levels, and restored the normal phenotype of CaMKIIdelta by reducing transcripts for delta4 and delta9 to levels present in WKY controls. Our data suggest the importance of specific changes in the CaMKII isoform composition for growth processes in the myocardium.