Octreotide in the treatment of thoracic duct injuries

Anecdotal reports support the use of octreotide in the treatment of traumatic thoracic duct injuries and chylothorax, but no prospective studies have proved its efficacy. We evaluated the effects of octreotide in treating thoracic duct transection in a canine model. Eight mongrel dogs (27.8+/-5.1 kg) were fed one pint of 10.5 per cent milkfat 2 hours before operation. Through a left supraclavicular neck incision, the thoracic duct was identified and transected, producing free flow of chyle. A quarter-inch drain was tunneled subcutaneously from the wound and attached to closed suction. After wound closure dogs were randomized to a control group (n = 4) receiving sham injections of saline subcutaneously three times per day, or a treatment group (n = 4) given 3 microg/kg octreotide three times per day. Postoperatively all dogs were fed a standard low-fat (5-7%) crude fat diet. Drain output was measured each day, and on odd-numbered postoperative days the drainage was analyzed for cholesterol, triglycerides, albumin, and total protein. Fistula closure was defined as drainage <10 ml/24-hour period. Treated dogs achieved fistula closure significantly faster than controls: 3.5+/-1.3 days versus 7.8+/-1.0 days (P = 0.0037). Whereas equivalent amounts of drainage occurred on the day of surgery and on postoperative day one in both groups, by postoperative day 2 the treatment group had significantly less drainage over 24 hours: 63+/-69 ml versus 195+/-79 ml (P = 0.046); this significant difference persisted through postoperative day 5 when drainage began to decrease in the control group. No significant differences between groups were seen in levels of cholesterol, triglycerides, albumin, or protein in the drainage at any time point. We conclude that octreotide is effective in treating thoracic duct injury, leading to an early decrease in drainage and early fistula closure. The mechanism for this effect remains to be clarified.     

The future of criminal violence: juveniles tried as adults

Juveniles tried as adults (JTA) represent a select and small subsample of juvenile offenders. This study seeks to provide a profile of habitually violent JTAs transferred to the adult penal system and to compare them with their adult counterparts. Twenty-nine incarcerated violent male juveniles tried as adults were compared with a sample of 27 incarcerated violent male offenders across demographic, neuropsychological, criminal history, psychopathy, and substance abuse variables. The JTAs were characterized by a high rate of gang membership (96%), substance abuse (alcohol, marijuana, and phenylcyclidene), and use of guns. In the juvenile sample, 65 percent used guns in violence not leading to arrest, and 93 percent used guns in a violent crime leading to arrest. Juvenile offenders were similar to their adult counterparts in patterns of criminality, although adult offenders had higher psychopathy scores. Both groups revealed generally intact neuropsychological functioning with the exception of a higher rate of perseverative responses in the adult sample. The results are discussed in terms of the implication of the degree of violence in a young offender population.     

C-C chemokine receptor 2 and sarcoidosis: association with Lofgren's syndrome

Sarcoidosis is thought to result from the interaction between an unknown environmental antigenic trigger and the host's genetic susceptibility. We hypothesized that sarcoidosis, or one of the disease subsets, could be associated with single nucleotide polymorphisms of C-C chemokine receptor 2 (CCR2) gene. Eight single-nucleotide polymorphisms in CCR2 were studied in a total of 304 Dutch individuals (90 non-L?fgren sarcoidosis, 47 L?fgren's syndrome, 167 control subjects). From the investigated CCR2 polymorphisms, nine haplotypes were deduced (haplotypes 1-9). In patients with L?fgren's syndrome, a strongly significant increase in the frequency of CCR2-haplotype 2, which includes four unique alleles (A at nucleotide position -6752, A at 3,000, T at 3,547, and T at 4,385), was observed compared with control subjects (74% vs. 38% respectively, p < 0.0001), whereas no difference was found between non-L?fgren sarcoidosis and control subjects (both 38%). The association between CCR2-haplotype 2 carriage frequency and L?fgren's syndrome (odds ratio, 4.4; p < 0.0001) remained significant after adjustment for human leukocyte antigen haplotype DRB1*0301-DQB1*0201 (odds ratio, 11.5; p < 0.0001) and female sex (odds ratio, 3.2; p = 0.003), two known risk factors for L?fgren's syndrome. In conclusion, this report describes a strong association between CCR2-haplotype 2 and L?fgren's syndrome. Further studies are needed to understand the molecular mechanisms underlying this association.     

Suppression of apoptosis in hematopoietic factor-dependent progenitor cell lines by expression of the FAC gene

Fanconi anemia (FA) is a genetically heterogeneous, inherited blood disorder characterized by bone marrow failure, congenital malformations, and a predisposition to leukemias. Because FA cells are hypersensitive to DNA cross-linking agents and have chromosomal instability, FA has been viewed as a disorder of DNA repair. However, the exact cellular defect in FA cells has not been identified. Sequence analysis of the gene defective in group C patients (FAC) has shown no significant homologies to other known genes. The FAC protein has been localized to the cytoplasm, indicating that FAC may either play an indirect role in DNA repair or is involved in a different cellular pathway. Recent evidence has indicated that FA cells may be predisposed to apoptosis, especially after treatment with DNA cross-linking agents. The demonstration that genes can suppress apoptosis has been accomplished by overexpression of such genes in growth factor-dependent cell lines that die by apoptosis after factor withdrawal. Using retroviral-mediated gene transfer, we present evidence that expression of FAC in the hematopoietic factor-dependent progenitor cell lines 32D and MO7e can suppress apoptosis induced by growth factor withdrawal. Flow cytometry and morphologic analysis of propidium iodide stained cells showed significantly lower levels of apoptosis in FAC-retroviral transduced cells after growth factor deprivation. Expression of FAC in both cell lines promoted increased viability rather than proliferation, which is consistent with other apoptosis-inhibiting genes such as Bcl- 2. These findings imply that FAC may act as a mediator of an apoptotic pathway initiated by growth factor withdrawal. Furthermore, the congenital malformations and hematologic abnormalities characterizing FA may be related to an increased predisposition of FA progenitor cells to undergo apoptosis, particularly in the absence of extracellular signals.     

Factors that affect human hemopoiesis are produced by T-cell growth factor dependent and independent cultured T-cell leukemia-lymphoma cells

Some laboratory results and clinical situations suggest that human T cells may be important in the regulation of growth of hematopoietic cells. Since the discovery of T-cell growth factor (TCGF), systems are now available for the long-term specific in vitro propagation of mature normal or neoplastic human T cells, providing an opportunity to study the influence of T cells on hematopoiesis. Recently, 24 cell lines from patients with cutaneous T-cell lymphoma (CTCL) and T-cell acute lymphoblastic leukemia (T-ALL) were grown with TCGF and then assessed for release of humoral factors that affect hematopoiesis. Conditioned media (CM) from these cell lines were tested for erythroid burst- promoting activity (BPA) and granulocyte colony-stimulating activity (CSA). BPA was detected in CM from 3/6 cultures of T-ALL patients and 4/6 CTCL cultures. CSA was found in the CM from 6/8 cultures of T-ALL patients, 7/12 CTCL cultures, and 3/4 CTCL cell lines that become independent of exogenous TCGF for growth. The CSA from several of the neoplastic T-cell cultures stimulated high levels of eosinophil colonies, a possible source of the eosinophilia seen in these patients. The ability of continuously proliferating human T lymphocytes, which retain functional specificity and responsiveness to normal humoral regulation, to produce factors that directly or indirectly stimulate myeloid and erythroid colony formation lends further credence to the role of T lymphocytes in regulating hematopoiesis.     

The Clara cell10 adenine38guanine polymorphism and sarcoidosis susceptibility in Dutch and Japanese subjects

CC10 (CC16, uteroglobin) is a pulmonary protein postulated to play a counter regulatory role in sarcoidosis pathogenesis. The adenine38guanine (A38G) polymorphism of the encoding CC10 gene (SCGB1A1) is functional. Recently, an association between the low CC10 producing 38A allele and sarcoidosis susceptibility has been reported in Japanese patients from Hokkaido. The aim of the present study was to confirm this association in a clinically well characterized population of Dutch white and Kyoto Japanese patients with sarcoidosis and control subjects. No difference in genotype or allele frequency was found between patients with sarcoidosis and control subjects in either ethnic population. Remarkably, however, a significant difference was found between the control subjects from Kyoto and Hokkaido, but not between the Japanese groups of patients with sarcoidosis. Furthermore, review of previously published A38G genotyping results showed a consistent difference in CC10 A38G allele frequencies between whites and Japanese subjects. We conclude that the CC10 A38G polymorphism does not influence sarcoidosis susceptibility in Dutch whites or in Japanese subjects from Kyoto. This stresses the importance of studying the influence of polymorphisms on disease susceptibility in multiple ethnically and geographically distinct disease and control populations before reaching conclusions.     

Safety and Efficacy of Intracoronary Thrombolysis as Adjunctive Therapy to Primary PCI in STEMI: A Systematic Review and Meta-analysis

BackgroundPrimary percutaneous coronary intervention (PPCI) is the preferred method of reperfusion in ST-elevation myocardial infarction. However, microvascular perfusion is often impaired due to distal embolization of thrombus. Intracoronary (IC) thrombolysis may attenuate thrombotic burden. We conducted a meta-analysis comparing the benefits and risks of IC thrombolytic therapy as an adjunct to PPCI.MethodsRandomized controlled trials (RCTs) were identified through search of Medline, EMBASE, Scopus, Web of Science, Cochrane Library (Cochrane Reviews and Cochrane Protocols), PROSPERO, and clinicaltrials.gov from 1946 to January 2019. Studies included patients with ST-elevation myocardial infarction undergoing primary PCI receiving IC thrombolytic agents. Both safety and efficacy outcomes were explored. Data were combined using a fixed-effects model.ResultsOf 1278 citations identified, 6 RCTs (890 patients; 519 IC thrombolytic and 371 IC placebo) were included. Post-PCI thrombolysis in myocardial infarction (TIMI) flow grade 2/3 occurred in 97.1% of the IC thrombolytic group vs 95.1% of the IC placebo group (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.28-1.17; P = 0.13). Complete ST-segment resolution was more common with IC thrombolysis (OR, 0.29; 95% CI, 0.15-0.57; P = 0.0003). There was a strong trend favouring fewer in-hospital major adverse cardiac events with IC thrombolysis when compared with IC placebo (OR, 0.64; 95% CI, 0.41-1.01; P = 0.05). There was no difference in bleeding (TIMI major, TIMI minor, and Bleeding Academic Research Consortium [BARC] 3-5 bleeds) between the 2 groups (OR, 1.36; 95% CI, 0.38-3.54; P = 4.84).ConclusionsGiven the limited studies to date, our meta-analysis suggests that a targeted IC thrombolytic approach is safe and potentially effective to augment PPCI. However, these findings deserve confirmation in a larger RCT.