Medical thoracoscopy with talc pleurodesis for refractory hepatic hydrothorax: A case series of three successes.

Medical thoracoscopy with chemical pleurodesis is a last resort for managing patients who suffer. from recurrent hepatic hydrothorax. However, despite pleurodesis, the rapid fluid build-up can hinder the successful apposition of the pleural surfaces. To improve the chances of success, we investigated the effectiveness of abdominal paracentesis before chemical pleurodesis via medical thoracoscopy to reduce significant fluid shifts from the peritoneal to the pleural cavity. We present a series of three patients with liver cirrhosis complicated by hepatic hydrothorax who underwent medical thoracoscopy with talc pleurodesis. Before the procedure, we optimised medical treatment, and if needed, we performed large-volume paracentesis to prevent rapid reaccumulation of pleural fluid. All study subjects achieved treatment success, defined as relief of breathlessness and absence of pleural effusion at 12 months. Complications related to the treatment included hepatic encephalopathy and acute kidney injury, which were managed conservatively. To manage symptomatic and recurrent hepatic hydrothorax, medical thoracoscopy with talc pleurodesis, preceded by the evacuation of ascites, can be considered as a treatment option. This procedure should be considered early for those who do not respond to medical management and are not suitable candidates for TIPS or liver transplantation.

A nationwide case-control study on cardiovascular and respiratory-related disorders in patients with gambling disorder in Sweden.

OBJECTIVES: We aimed to examine potential relationships and gender differences between cardiovascular disease (CVD), diabetes, obesity, respiratory-related disorders, and gambling disorder (GD). We hypothesized that (1) GD patients would be more likely than controls to have CVD, diabetes, obesity, and respiratory-related diseases; and (2) females with GD would be more likely than men with GD to have CVD, diabetes, obesity, and respiratory-related diseases. STUDY DESIGN: National retrospective case-control study. METHODS: We used data from the Swedish National Board of Health and Welfare between 2005 and 2019. A total of 10,766 patients were included, and 3592 of them had GD. Every GD patient was matched with two age- and gender-matched controls. Patient data, including the history of medical diagnoses, were extracted. Descriptive statistics, Chi-squared and Fisher's exact tests were used to compare GD patients and controls. RESULTS: GD patients had a higher prevalence of CVD and respiratory-related disorders than controls. Diabetes rates were 5% for GD patients and 2% for controls; CVD (18% vs 12%); respiratory-related disease (7% vs 4%); and obesity (7% vs 3%). Women with a diagnosis of GD have a higher prevalence of obesity and somatic comorbidities other than diabetes compared to men. CONCLUSIONS: This is the largest case-control study conducted to date showing GD patients have a higher prevalence of CVD, diabetes, obesity, and respiratory-related disorders than controls. Women with GD appear to be more susceptible than men to CVD, obesity, and respiratory-related disorders; however, this may be partially explained by differences in help-seeking behavior. Thus, our findings highlight the importance of early identification of GD patients who may also have somatic conditions requiring treatment. This can be accomplished by implementing a screening program for GD, CVD, diabetes, obesity, and respiratory-related disorders, and by including healthy lifestyle management strategies.

The cost of foreign body injuries in the upper aero-digestive tract: need for a change from a clinical to a public health perspective?

OBJECTIVE: This paper addressed the impact in terms of direct costs of the injuries in children due to foreign bodies in the upper aero-digestive tract. METHODS: Two thousand one hundred and three consecutive cases were collected from 2000 to 2002 in 16 European hospitals, 1 hospital for each participating country, and referred to children aged until 14 who had FB injuries. Costs were based on the extraction of the FB procedures and on hospitalization length, based on DRGs. Determinants of costs and of length of stay (LOS) were analyzed using a multilevel model. RESULTS: The major cost of the treatment of FB injuries is covered by the ENT Departments, which are usually the first choice of referral, directly from the patients. Children had a mean LOS of 2.13 days (95% C.I. 1.99-2.29). Treatment of the FB was associated with a mean cost of euro 1017.37 (95% C.I. 963.27-1073.51). In the multivariable analysis higher costs are related to the modality of arrival to the hospital by walk, to the site of the injury (ICD-933, ICD-934, ICD-935 in particular) and to the use of surgery in removing the FB. DISCUSSION: Foreign bodies injuries are posing a great threat not only with regards to the clinical aspects but also from the public health perspective, their treatment being associated with high costs, in particular when surgery is needed.

Phase II study of pegylated liposomal doxorubicin HCl (Caelyx) in combination with cyclophosphamide and vincristine as second-line treatment of patients with small cell lung cancer.

BACKGROUND: Despite chemotherapy and radiotherapy for small cell lung cancer (SCLC), most patients die within 2 years. Response rates for second-line chemotherapy are 15-25%, with a median survival of 5 months. Caelyx, a pegylated liposomal formulation of doxorubicin, may be better tolerated and has activity in SCLC. PATIENTS AND METHODS: Thirty-two patients were enrolled in a phase II study of intravenous Caelyx (35 mg/m2), cyclophosphamide (750 mg/m2) and vincristine (1.2 mg/m2) every 21 days as second-line therapy in SCLC for up to six cycles. RESULTS: Thirty patients were evaluable for response, with a response rate of 10%. Another two had an unconfirmed response. Stable disease (SD) for >or=2 cycles was seen in an additional 53%. Grade 3 or 4 non-hematologic toxicity was seen in 17 (55%) patients (26 [22%] cycles) and included fatigue, mucositis, plantar-palmar erythrodysesthesia, rash and neuropathy. Twelve patients required transfusions. All patients on study have now expired, with a median survival of 28 weeks (7 months). For patients with SD or partial response, median time to progression was 15 weeks. CONCLUSION: The combination of Caelyx, cyclophosphamide and vincristine, despite cyclophosphamide and Caelyx dose reductions, has modest activity in relapsed SCLC with acceptable toxicity.

Metabolism and disposition of 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) in rhesus monkeys.

Metabolism and disposition of the tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent rodent lung carcinogen, were studied in rhesus monkeys. In three males receiving a single i.v. dose of [5-3H]NNK (0.72 mCi; 4.6-9.8 microg/kg), urine was collected for 10 days. Within the first 24 h, 86.0 +/- 0.7% of the dose was excreted. NNK-derived radioactivity was still detectable in urine 10 days after dosing (total excretion, 92.7 +/- 0.7%). Decay of urinary radioactivity was biexponential with half-lives of 1.7 and 42 h. Metabolite patterns in urine from the first 6 h closely resembled those reported previously for patas monkeys; end products of metabolic NNK activation represented more than 50% of total radioactivity. At later time points, the pattern shifted in favor of NNK detoxification products (60-70% of total radioactivity in urine), mainly 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its O-glucuronide conjugates. One female rhesus monkey received a single i.v. dose of [5-3H]NNK (1.72 mCi; 28.4 microg/kg) under isoflurane anesthesia; biliary excretion over 6 h (0.6% of the dose) was 10 times less than predicted by our previously reported rat model. No preferential excretion of NNAL glucuronide was observed in monkey bile. Collectively, these results suggest that the rhesus monkey could be a useful model for NNK metabolism and disposition in humans.

Studies on pyrazinoylguanidine. 3. Downregulation of lipolysis in isolated adipocytes.

The effects of pyrazinoylguanidine (PZG) on lipolysis and intracellular cyclic AMP concentrations were investigated in isolated rat adipocytes. PZG reduced basal cyclic AMP concentrations and blocked in a concentration-dependent manner forskolin (1 mumol/l) and isoproterenol (1 mumol/l) stimulatory effects on intracellular cyclic AMP production and lipolysis. PZG's effects on hormone-sensitive lipase were investigated in the presence and absence of glucagon (1 mumol/l) or isoproterenol (1 mumol/l). PZG inhibited uncompetitively the induction of hormone-sensitive lipase by either glucagon or isoproterenol. PZG's antilipolytic effects appeared to result from downregulation of intracellular cyclic AMP concentrations. In adipose tissue, cyclic AMP controls lipolysis through hormone-sensitive lipase. PZG's downregulation of lipolysis and cyclic AMP concentrations was unaffected by adenosine deaminase or pertussis toxin, suggesting that PZG did not activate Gi, the inhibitory guanyl nucleotide regulatory protein.

Studies on pyrazinoylguanidine. 4. Upregulation of phosphodiesterase activity in rat adipose tissue and downregulation of gluconeogenesis and adenosine 3',5'-monophosphate concentrations in perfused rat liver.

In isolated rat adipocytes stimulated with theophylline (1 mmol/l), pyrazinoylguanidine (PZG) downregulated both lipolysis and cyclic AMP concentrations, raising the possibility that PZG stimulates adipose insulin-sensitive phosphodiesterase. To investigate this directly, we measured PZG's effects on phosphodiesterase activity in rat adipocytes. PZG (10 mumol/l) as well as insulin (0.1-1 mU) increased adipose phosphodiesterase activity, whereas theophylline reduced it. Also investigated were PZG's effects on gluconeogenesis and cyclic AMP in perfused rat liver where PZG decreased gluconeogenesis and cyclic AMP concentrations.

Studies on pyrazinoylguanidine. 1. Characterization of metabolic effects in diabetic rats.

Pyrazinoylguanidine (PZG) is a new antihyperglycemic, antihyperlipidemic drug. The current study reports on the development of an animal model in which the favorable metabolic effects of PZG, previously described in diabetic patients, could be reproduced and investigated. Adult male as well as female Sprague-Dawley rats received a single intraperitoneal dose (50 mg/kg) of streptozotocin (STZ). One week later, they received PZG (50 mg/kg i.p.) twice daily for a week. Compared to vehicle (saline-treated controls), PZG reduced plasma concentrations of glucose by 33-70%, triglycerides by 50-70%, nonesterified fatty acids by 17-27%, cholesterol by 10-50%, and glucagon by 18-20%. Hydrochlorothiazide given in a dose of 20 mg/kg i.p. b.i.d for 1 week induced metabolic effects opposite to those of PZG. In the Zucker fatty rat, PZG also lowered plasma glucose and lipid concentrations. These results indicate that PZG ameliorated the abnormalities of plasma glucose and lipid that characterize STZ-diabetic and Zucker fatty rats.

Studies on pyrazinoylguanidine. 2. Comparative drug and dose effects on glucose and lipid metabolism in streptozotocin-induced diabetic rats.

In streptozotocin (STZ)-induced diabetic rats, pyrazinoylguanidine (PZG) markedly reduced elevated fasting concentrations of plasma glucose, triglycerides, and cholesterol. In contrast, these parameters were unaffected by a sulfonylurea, glyburide, or by a biguanide, metformin. PZG's glucose- and lipid-lowering effects were dose-dependent. These metabolic effects were also investigated after: (a) pyrazinoic acid (PZA), a metabolite of PZG; (b) 3-amino-PZG, an analog of PZG, and (c) 3-amino-PZA, a hydrolytic product of 3-amino-PZG. PZA moderately reduced elevated fasting glucose and lipid concentrations in STZ-diabetic rats, suggesting partial medication of PZG's antidiabetic actions by PZA. Neither 3-amino-PZG nor 3-amino-PZA exerted any glucose- or lipid-lowering effect in STZ-diabetic rats.

Effects of low molecular weight B-cell growth factor on proliferation of leukemic cells from children with B-cell precursor-acute lymphoblastic leukemia.

Recently, low-molecular-weight B-cell growth factor (LMW-BCGF) has been reported to stimulate growth of leukemic cells from B-cell precursor-acute lymphoblastic leukemia (BCP-ALL). We further investigated the effects of LMW-BCGF on proliferation of leukemic clonogenic (progenitor) and nonclonogenic (progeny) cells from children with BCP-ALL (28 patients) and B-cell ALL (two patients). Patients were either at diagnosis (n = 18) or in relapse (n = 12). Response of leukemic progenitor cells was determined by culturing cells (10(5) cells/mL) in methylcellulose with 0.1 U/mL LMW-BCGF. Colonies (greater than 20 cells) were counted at day 7. The response of the leukemic progeny population was determined by DNA synthesis studies using tritiated-thymidine and by DNA quantitation with propidiumiodide for determination of cell-cycle status. LMW-BCGF supported growth of leukemic progenitor cells from 20 of 28 (71%) BCP-ALL and two of two B-cell ALL patients. Colony numbers ranged from 7 to 2,400 (mean 145, median 45). A dose-response effect in colony growth was noted, with an apparent plateau at approximately 2.0 U/mL LMW-BCGF. Colony cells were primarily of leukemic phenotype (CD19+/CD10+/-). LMW-BCGF also induced significant increases in leukemic progeny cell proliferation as measured by both thymidine incorporation (stimulation indexes of 1.6 to 34) and by cell-cycle assay (percentage S+ G2/M stimulation indexes of 1.6 to 6). LMW-BCGF was more effective in stimulating leukemic proliferation than three recombinant interleukins (rIL-2, rIL-3, rIL-4), although rIL-3 was able to support colony growth in 4 of 11 patients. These results indicate that LMW-BCGF and, to a lesser degree rIL-3, are able to stimulate proliferation of BCP-ALL progenitor and progeny cells, whereas rIL-2 and rIL-4 do not support progenitor cell proliferation and have only marginal effects on leukemic progeny cell proliferation.