Differential diagnosis of apneas in preterm infants

Clinically relevant apneas, which are common in preterm infants, may adversely affect later neuropsychological condition in this group of patients. Pharmacotherapy to stimulate respiratory functions may be unsuccessful. Polygraphic recording may help in the differential diagnosis of these clinically relevant events. Twenty-nine preterm neonates born before 36 weeks of gestational age were examined using polygraphic recording (respiration—two channels, perioral electromyography, oxygen saturation, heart rate, electroencephalography, electrocardiography, electrooculography). The examination was ordered by the attending physician after an unsuccessful treatment of apnea by Aminophylline, and it should contribute to the clarification of the causes of these events. In the course of the polygraphic examinations, altogether 63 episodes were recorded during which the pulse oximeter alarm signal was set off. In 42 cases, the alarm signal was set off in events during which SaO₂ fell below 85%. In the remaining 21 cases, the alarm signal was set off in episodes during which early bradycardia below 90/min occurred. The onset of apnea was very often associated with the phasic increase of the perioral electromyography and with electroencephalography arousal reaction. Because of suspicion that these apneas may be triggered by episodes of gastroesophageal reflux, the interruption of the Aminophylline treatment and setting up an antireflux regimen were recommended. These therapeutic measures had a positive effect: The frequency of alarm signals decreased within 48 h by a statistically significant 50%. In cases where the pharmacotherapy of apnea by stimulation of respiratory functions is not successful, differential diagnostic analysis should be performed. Polygraphy may contribute to the clarification of the causes underlying clinically relevant apneas in a view of newly described polygraphic signs. It is feasible to suspect, based on these signs, that gastroesophageal reflux is the cause for clinically significant apneas in that case.     

Repeated chemosensitivity testing in patients with epithelial ovarian carcinoma

Epithelial ovarian carcinoma (EOC) is a highly chemosensitive tumor, but most patients with advanced EOC initially responding to first-line chemotherapy will eventually relapse. Chemosensitivity testing may offer an opportunity for the optimal selection of chemotherapeutic agents for individual patients. In the present retrospective analysis we have examined the changes in chemosensitivity profiles during the course of the disease. Chemosensitivity was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Two or more samples at least 14 days apart were obtained from 34 patients with ovarian cancer. Chemoresistance increased significantly at the second measurement only for paclitaxel and carboplatin, the most frequently used cytotoxic drugs. No significant difference compared to baseline was observed at subsequent measurements for any other cytotoxic agent studied, although a non-significant trend for increased chemoresistance was observed. In conclusion, in the present cohort only paclitaxel and carboplatin chemosensitivity changed significantly, although to a limited extent, during the course of the disease. In contrast to a limited increase of paclitaxel and carboplatin chemoresistance, no significant changes were observed for other cytotoxic agents examined. The present data indicate that chemoresistance increases, to a modest extent, against the drug most frequently used, but remains relatively stable during the course of disease, especially for agents that are not used in the therapeutic regimen.     

Congenital diaphragmatic hernia: onset of respiratory distress and size of the defect

The purpose of this study was to evaluate the outcome in neonates with congenital diaphragmatic hernia (CDH) either presenting within the first 24 h of life or diagnosed prenatally. The study was particularly focused on the time of onset of respiratory distress and on the use of the Gore-Tex (GT) patch for diaphragmatic reconstruction. Records of 104 neonates with CDH were retrospectively reviewed. The data were analyzed by ANOVA, Kruskal–Wallis test or χ ² test as appropriate. The result showed that the overall survival rate was 73.1% (76/104). Survival of operated neonates was 91.6% (76/83). Postnatally diagnosed neonates with the onset of respiratory distress within the first minute of life survived in 67%, with the onset between 2 and 10 min survived in 89%, whilst neonates with the onset of respiratory distress after l0 min survived in 100% (P = 0.007). Birth weight, gestational age, time of onset of respiratory distress and Apgar score significantly differed between survivors and nonsurvivors. Primary closure of the diaphragmatic defect was performed in 62 patients while the GT patch was used in 21 patients. The survival of patients with a large defect treated with a GT patch was lower (76.2 vs. 96.8%, P = 0.003). There was only one case of recurrence in our series with the GT patch. Survival depends on the time of onset of respiratory distress and size of the defect, both of which correlate with the degree of pulmonary hypoplasia. The term high-risk CDH is appropriate only for children with respiratory distress within the first 10 min of life and those diagnosed prenatally. The GT patch is a suitable material for the diaphragmatic reconstruction; we suppose that the recurrence is caused by incorrect attachment of the patch to the thoracic wall.     

Pegylated liposomal doxorubicin in combination with hyperthermia for treatment of skin metastases of breast carcinoma: a case report.

BACKGROUND: Incorporation of doxorubicin hydrochloride into pegylated liposomes (PLD) may decrease chemotherapy side effects and increase the activity. Hyperthermia could further potentiate its effectiveness. CASE REPORT: A patient with skin metastases of breast carcinoma was treated with intravenous infusion of PLD (Caelyx) in combination with ultrasound hyperthermia. Each cycle consisted of infusion of 40 mg PLD absolute dose, followed by 2 fractions of hyperthermia 41-43 degrees C for 45 min 1 and 48 h after infusion. A complete remission was observed after the combination treatment with no significant toxicity. CONCLUSION: Present observations suggest that the combination of PLD with hyperthermia of skin metastases of breast carcinoma may be an active and well tolerated treatment.     

Pathological complete response after primary chemotherapy in a mother and daughter with hereditary breast carcinoma: two case reports

The prognosis of patients with BRCA1-related breast carcinomas is inferior to the patients without BRCA1 mutation, but most of these tumors have a so-called triple negative phenotype characterized by increased chemosensitivity. Information regarding the chemosensitivity of BRCA1-related breast carcinomas is limited. We present a case of a mother and daughter with hereditary breast carcinoma treated with primary chemotherapy using the dose-dense combination of doxorubicin and cyclophosphamide and sequential weekly paclitaxel administration. Pathological complete response was observed in both patients. Subsequent genetic analysis revealed the same BRCA1 mutation with exon 5-14 deletion in both women. The present experience as well as other reports indicate increased sensitivity of BRCA1-related breast carcinoma to primary chemotherapy.     

Electrophysiological measurements of the stria vascularis potentials in vivo

Glass microelectrodes were introduced into the stria vascularis (SV) to measure the DC potential profile of the SV in vivo from its apical as well as basal side. The K+ concentration gradient in the lateral cochlear wall was measured by means of double barrel K+-selective microelectrodes. A positive potential 10.4 +/- 6.3 mV higher than the endocochlear potential (EP) was found in the SV. In noise-exposed animals the positive potential found in the SV was 14.6 +/- 7.2 mV higher than the EP. K+ concentration observed during penetration into the SV was in the range of 50-100 mmol/l. Simultaneous measurement of the DC positive potential in the SV and EP showed a nearly parallel time course during anoxia with a tendency to increase the difference between the SV potential and the EP. The difference reached approximately 30 mV 20 min after the beginning of anoxia. It may be assumed that the electrogenic pump localized at the basolateral membrane of the marginal cell (MC) is a source of the positive potential inside the MC and is hence a source of the potential drop across the luminal side of the MC membrane.     

Large,detergent-resistant complexes containing murine antigens Thy-1 and Ly-6 and protein tyrosine kinase p56lck

A number of human and mouse leukocyte surface (glyco)proteins anchored in a membrane via glycosylphosphatidylinositol (GPI) moiety have been previously shown to be noncovalently associated with protein tyrosine kinases (Science 1991. 254: 1016; J Biol. Chem. 1992. 267:12317). Here we show that two murine antigens of this group, Thy-1 and Ly-6, implicated in the activation of the T cells, are associated with each other, with the kinase p56^lck and with several of potential kinase substrates in very large, detergent-resistant complexes, the size of which is between 50 and 200 nm, as determined by ultrafiltration and gel chromatography. Experiments on simultaneous solubilization of mixed human and mouse cells rule out that the observed complexes are artifacts induced by the detergent. Complexes of similar composition and properties were obtained when either detergents Brij-58, Nonidet-P40 or 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane-sulfonate (Chaps) were used for solubilization of the cells, while octylglucoside at least partially dissociated them. These “GPI-complexes” may be essential for the well-known signal-transducing capacity of Thy-1 and Ly-6.     

Urea and creatinine levels in saliva of patients with and without periodontitis

Despite the fact that saliva contains measurable concentrations of urea and creatinine, it is not widely used in clinical nephrology. One of the reasons is the high inter‐ and intra‐individual variability in the salivary markers of kidney function. We hypothesized that gingival bleeding in patients with periodontitis could contribute to this variability by increasing the concentration of salivary urea or creatinine. Samples were collected from 25 patients with periodontitis and 29 healthy controls. In addition, saliva samples from five healthy volunteers were artificially contaminated with blood. The concentration of urea, but not that of creatinine, was more than twice as high in patients with periodontitis than in controls. Artificial contamination of saliva with blood did not affect the salivary concentration of creatinine. Salivary urea increased only with very high levels of contamination (≥2.5% blood in saliva), but that did not occur in patients. In conclusion, periodontitis increases the concentration of salivary urea, but this is not likely to be a result of contamination with blood. Future studies should investigate the composition of the oral microbiome, specifically regarding how it affects the concentration of salivary urea. Salivary creatinine seems to be a more robust non‐invasive marker of renal functions than salivary urea.     

Pharmacological strategies for detoxification

Detoxification refers to the safe discontinuation from a substance of dependence and is distinct from relapse prevention. Detoxification usually takes between a few days and a few weeks to complete, depending on the substance being misused, the severity of dependence and the support available to the user. Psychosocial therapies alongside pharmacological treatments are essential to improve outcome. The dependencies considered in this overview are detoxification from opioids (with methadone, buprenorphine, α₂-adrenoceptor agonists and adjunct medications), alcohol (with benzodiazepines, anti-glutamatergics and γ-aminobutyric acid (GABA)-ergic drugs), stimulants and cannabis (with no clear recommended pharmacological treatments), benzodiazepines (with dose tapering) and nicotine (with nicotine replacement therapy, antidepressants and partial agonists). Evidence is limited by a lack of controlled trials robust enough for review bodies, and more research is required into optimal treatment doses and regimes, alone and in combination.