Stimulation of tear secretion by topical agents that increase cyclic nucleotide levels

The authors examined the effect of topical application of agents known to increase cyclic nucleotide levels on tear secretion by accessory lacrimal gland tissue in their rabbit model for keratoconjunctivitis sicca (KCS). Tear secretion was studied by changes in tear film osmolarity and tear volume caused by application of the agents relative to application of isotonic buffer solution alone. A decrease in tear film osmolarity or increase in tear volume was interpreted as an increase in tear secretion. Irritative stimulation was distinguished from pharmacologic stimulation by the prior use of topical proparacaine. The following agents significantly decreased tear film osmolarity and increased tear volume: vasoactive intestinal peptide (2 X 10(-8) to 2 X 10(-6) M); three pro-opiomelanocortin fragments alpha-, beta-, and gamma-melanocyte stimulating hormone at 10(-4), 10(-3), and 10(-3) M, respectively; the permeable cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) analogs 8-Br cAMP (0.3-3.0 X 10(-3) M) and 8-Br cGMP (1.0-10.0 X 10(-3) M); and the cyclic nucleotide phosphodiesterase inhibitor 1-isobutyl-3-methyl xanthine (0.3-3.0 X 10(-3) M). Forskolin (2 X 10(-4) M), which activates the catalytic subunits of adenyl cyclase, increased tear volume significantly. Secretin, adrenocorticotropic hormone, and pilocarpine were ineffective. The authors conclude that agents that increase either cAMP or cGMP levels pharmacologically stimulated tear secretion when applied topically to rabbit eyes with surgically induced KCS.     

Brain type creatine kinase in relation to oxygen desaturation in the blood of children with congenital heart disease

The concentration of brain type creatine kinase (CK-BB) was measured in blood from the internal jugular vein in 32 children (less than 1 year old) with congenital heart disease. In transposition of the great arteries the CK-BB levels were significantly higher than in children without cyanosis (10.1 +/- 4.1 vs. 3.0 +/- 0.5 ng/ml). A negative correlation was found for CK-BB concentration and arterial oxygen saturation (r = -0.41, p less than 0.02 for all children and r = -0.62, p less than 0.05 for those with tetralogy of Fallot). It is suggested that the increased CK-BB levels in the blood of cyanotic children reflect chronic cerebral hypoxia, which may explain other reports of reduced psycho-intellectual function in patients with cyanotic heart disease.     

Trapeziometacarpal joint osteoarthritis: a retrospective study comparing arthrodesis to tendon interposition arthroplasty

Abstract Surgical management of trapeziometacarpal joint osteoarthritis (OA) is still controversial. The aim of this study was to evaluate and compare results of trapeziometacarpal arthrodesis and of tendon interposition arthroplasty. One hundred twenty-six patients suffering from trapeziometacarpal OA underwent surgery between 1996 and 2001. Of these patients, 62 (78 thumbs) treated with joint arthrodesis and 33 (41 thumbs) treated with tendon interposition arthroplasty with abductor pollicis longus (APL) have been evaluated at follow-up and therefore entered this study. Mean age was 53 years, while the mean follow-up was 36 months. Overall results were satisfactory in 84 patients with good pain improvement. Patients treated with arthrodesis showed better functional ability in bi-digital pinch and grip strength. First finger opposition motion, however, was better conserved in patients treated with interposition arthroplasty. Fusions had an 11.5% complication rate (9 thumbs) with nonunions, whereas 14.8% (6 thumbs) of patients treated with interposition arthroplasty developed 1 first metacarpal base collapse, resulting in 1 first ray length reduction. Despite complications, however, patients did not report unsatisfactory results and generally experienced marked pain reduction. This study shows that arthrodesis can be considered the treatment of choice in patients suffering from trapeziometacarpal OA at Eaton stage III or less, whatever the age and when a good pinch strength is needed.     

Genetic abnormalities and CNS tumors: report of two cases of ependymoma associated with Klinefelter’s Syndrome (KS)

Objects Genetic syndromes associated with ependymoma are uncommon, with the exception of NF2. We describe two cases of ependymoma presenting with Klinefelter’s Syndrome (KS) as co-morbid condition. Materials and methods The first patient was diagnosed for KS during pregnancy; he also presented a thyroid agenesis and a deficit of methyltetrahydrofolate reductase (MTHFR); at 30 months of age he was operated on for a grade II ependymoma of IV ventricle; after a multiple-stage surgery, he underwent oral chemotherapy and stereotactic radiotherapy, but after 15 months he presented a local recurrence and died. The second patient was diagnosed for KS at the age of 16 months; at 10 years of age, due to back pain, he underwent an MRI, which showed a cauda equine tumor. He underwent surgery and radiotherapy. Histology was of mixopapillary ependymoma. Conclusion In a review of literature, various neoplasms have been described in association with KS. To our knowledge, these are the first two cases reported of ependymoma associated to KS. A retrospective study of 44 monoinstitutional ependymoma cases demonstrated association with genetic syndromes in 22%.     

Management of bowel obstruction in advanced and terminal cancer patients

Background: Bowel obstruction is a common and distressing outcomein patients with abdominal or pelvic cancer. Patients and methods: Patients may develop bowel obstructionat any time in their clinical history, with an incidence rangingfrom 5.5% to 42% in ovarian carcinoma and from 10% to 28.4%in colorectal cancer. The causes of the obstruction may be benignpostoperative adhesions, a focal malignant or benign deposit,relapse or diffuse carcinomatosis. The symptoms which are almostalways present are intestinal colic (reported in 72%–76%of patients), abdominal pain due to distension, hepatomegalyor tumor masses (in 92% of patients) and vomiting (68%–100%)of cases. Conclusion: While surgery must remain the primary treatmentfor malignant obstruction, it is now recognised that there isa group of patients with advanced disease or poor general conditionwho are unfit for surgery and require alternative managementto relieve distressing symptoms. A number of treatment optionsare now available for the patient with advanced cancer who developsintestinal obstruction. In this review of the literature, theindications for surgery will be examined, the use of nasogastrictube and percutaneous gastrostomy evaluated and the place ofdrugs for symptom control described. bowel obstruction, advanced and terminal cancer patients     

Acetaldehyde, ethanol and acetone concentrations in blood of alcohol-treated mice receiving aldehyde dehydrogenase-loaded erythrocytes.

Blood levels of acetaldehyde (ACh), ethanol and acetone were investigated in mice treated with ethanol for 6 months and receiving compatible erythrocytes (RBCs) overloaded with aldehyde dehydrogenase (AlDH). Following an acute dose of ethanol, ACh levels were significantly lower in these animals than in alcohol-treated mice receiving AlDH-unloaded RBCs, and were similar to the ACh levels of normal mice. The peak ethanol concentration was higher in normal mice than in both groups of alcohol-treated animals, while acetone concentrations were not significantly different in the three groups of animals.     

The pharmacokinetics of lignocaine in humans during a computer-controlled infusion.

Several types of chronic pain syndromes are effectively treated with sodium channel blockers such as lignocaine. Further investigation of this therapeutic modality would be facilitated by refinement of the parameters describing lignocaine distribution and elimination. This would allow precise lignocaine infusion by a computer-controlled infusion to attain and maintain stable target lignocaine concentrations. Arterial blood samples were obtained at frequent intervals during a computer-controlled infusion of lignocaine in 12 adult human volunteers. Plasma lignocaine concentrations of 1, 2, 3, 4 and 5 microg/ml were targeted for 15 min at each concentration. A three-compartment mammillary pharmacokinetic model best described the resulting concentration vs time profile. A population pharmacokinetic analysis was performed using three different techniques; the two-stage, pooled and mixed effects modelling. There was marked overshoot of the plasma concentration above the target prior to refinement of the pharmacokinetic parameters. The best parameters of a three-compartment mammillary model fit to the measured concentration using the pooled data approach were: V(1) = 7.44, V(2) =11.5 and V(3) = 97.71; Cl(1) = 0.585, Cl(2) = 2.23 and Cl(3) =1.64 l/min. Similarly calculated parameters using NONMEM were V(1) = 6.99, V(2) =12.2 and V(3) =1341; Cl(1) = 0.703, Cl(2) =1.24 and Cl(3) =1.49 l/min. The addition of age as a covariate of the pharmacokinetic parameters improved the model in both cases. Height, lean body mass and body surface area as covariates of the pharmacokinetic parameters did not improve the predicted value of the model. Prospective testing of the pharmacokinetic parameters will be required to define whether they function well. The refinement of pharmacokinetic parameters for the computer-controlled intravenous infusion of lignocaine will facilitate further research in pain therapy. Published lignocaine pharmacokinetic values have a relatively large central volume of distribution, and hence, when implemented as a computer-controlled infusion, result in dramatic overshoot shortly after targeting a higher plasma concentration. In light of the long-lasting pain relief provided by sodium channel blockade in neuropathic pain states, overshoot of plasma concentrations must be avoided if the concentration vs effect relationship is to be defined.     

Reducing the Occupational Risk of Infections for the Surgeon: Multicentric National Survey on More Than 15,000 Surgical Procedures

The objective of this study was to find the incidence of accidental exposures to blood and body fluids among surgeons during operations and to describe their dynamics. A probabilistic model was also used to predict the cumulative 30-year risk to the surgeon of contracting hepatitis B and C viruses (HBV, HCV) or human immunodeficiency virus (HIV) infection and estimate the effect of preventive strategies in reducing this risk. A multicentric prospective survey, based on self-administered questionnaires, was conducted during a period of 6 months in 39 Italian hospitals. An accidental exposure to blood or body fluids occurred in 9.2% of 15,375 operations. In about 2% of procedures a parenteral-type injury, such as actual skin puncture or eye contamination, was suffered by the operating surgeon. A needle-stick injury was the commonest accident, and its occurrence was found to vary with the phase of the procedure and its length. The current lifetime risk of acquiring HBV, HCV, and HIV infection in our regions was estimated to be as high as 42.7%, 34.8%, and 0.54%, respectively. The adoption of preventive strategies is expected to reduce this risk to 21% for HBV, 16.6% for HCV, and 0.23% for HIV infection. Active immunization of surgeons against HBV is strongly recommended. The case is also made for the use of a face-shield combined with a permanent change in our surgical practice capable of reducing the current high rate of parenteral injuries.     

Dystonic attacks related to sleep and exercise.

Two unrelated children displayed attacks of paroxysmal jerky 'puppet-like' movements lasting 2-3 min. The attacks were not kinesigenic and occurred during wakefulness precipitated by physical exercise and during NREM sleep, spontaneous or upon arousal and awakenings. Paroxysmal dystonic choreoathetosis was excluded by the absent family history, and paroxysmal kinesigenic dystonia by the absence of triggering effects by sudden movements and efficacy of anticonvulsants. Pattern and duration of involuntary movements were not those typical of nocturnal paroxysmal dystonia. Our cases emphasize that overlap exists among the different clinical categories of paroxysmal dyskinesia.