TRANSFORMING GROWTH FACTOR-α EXPRESSION IS ALTERED DURING EXPERIMENTAL HEPATOCARCINOGENESIS

In order to characterize the role of transforming growth factor-α (TGFα) during hepatocarcinogenesis, liver tissue was examined at 10, 16, and 19 weeks following initial 10-week diethylnitrosamine (50 mg l⁻¹ drinking water) exposure in female Wistar rats. Liver tissue protein extracts were electrophoresed and transferred to nitrocellulose filters. Levels of tissue-derived TGFα and epidermal growth factor receptor (EGFr) were assessed using an anti-TGFα monoclonal antibody (Ab-1) and an anti-EGFr polyclonal antibody (AB-4), coupled with scanning densitometric quantification. Immunolocalization of TGFα was performed in Bouin's-fixed, paraffin-embedded liver tissue sections. The distribution and intensity of TGFα immunoreactivity varied according to the degree of dysplasia, severely dysplastic cells being strongly immunoreactive. At week 10, mild hepatocyte dysplasia and perivenular inflammation were evident, together with a corresponding increase in perivenular TGFα immunoreactivity. By week 16, foci of moderate to severe dysplasia were observed; at this stage, there was a decrease in perivenular immunoreactivity but a further increase in overall liver tissue TGFα levels. Some ‘altered foci’ and dysplastic nodules showed intense immunoreactivity for TGFα. At these time points, immunodetectable liver EGFr was found to decrease significantly in comparison with normal control tissue. TGFα immunoreactivity was observed in fully developed carcinomas at week 19, although some tumours were negative by immunohistochemistry. The up-regulation of immunodetectable TGFα and the concomitant down-regulation of EGFr demonstrated positive ( P <0·01) and negative ( P <0·001) correlations, respectively, with hepatocyte proliferation indices. These findings suggest that the TGFα/EGFr ligand receptor system may be important during tumour promotion and in the stimulation of continued proliferation in hepatocellular carcinomas.     

Salivary bacteria and oral health status in children with disabilities fed through gastrostomy

International Journal of Paediatric Dentistry 2010; 20: 179–185 Objectives. This study examined caries level, amount of calculus, and oral microbial environment in gastrostomy tube (GT)‐fed children compared with healthy children and children with disabilities orally fed (PO). Study design. The study group consisted of 12 GT‐fed children and the two control groups consisted of 16 children with disabilities orally fed and 17 healthy children. DMF‐T/dmf‐t index, calculus index, Mutans Streptococci (MS), Lactobacilli (LB) levels and salivary buffer capacity were examined. Results. DMF‐T/dmf‐t index was significantly lower in the tube‐fed group. Calculus index was highest in the tube‐fed group. MS and LB levels were the lowest in the tube‐fed children. Correlation was found between MS and DMF‐T/dmf‐t. Conclusions. Tube‐fed children demonstrated significantly higher calculus levels and less caries, MS, and LB levels then healthy children or children with disabilities eating PO.     

Impairment of Red Cell Viability by Exposure to "Excess" Acid--Citrate Dextrose

Collection of blood in "excess" ACD leads to a loss of red cell viability whenthe blood is transfused back into the donor, even without any appreciablestorage period. The mechanism of this loss of viability is not clear. The loss isaccentuated by incubation at 37 C.; it is not affected by varying the dextroseconcentration of the ACD; it cannot entirely be attributed to change in pH ofthe final suspension medium; and it is not related to the degree of swelling ofthe red cells. The loss of viability can completely be corrected by the additionof small amounts of chloride to the ACD.

This effect is presumably the same as the "lesion of collection" described byGibson et al. in relation to viability studies after 28 days of storage.⁴

Submitted on September 27, 1965 Accepted on February 6, 1966     

EPIDEMIOLOGY OF ALCOHOLIC CIRRHOSIS

Seventy-seven alcoholic patients, 54 men and 23 women, had cirrhosis of the liver when they first attended the Alcoholism Clinic at St Vincent's Hospital, Melbourne, between July, 1964, and June, 1968. During this period 800 chronic alcoholics, 663 men and 137 women, attended the clinic. Cirrhosis was thus diagnosed twice as often in women as in men. The case histories of the 77 cirrhotic patients were reviewed, and information was collected about socio-economic status and drinking habits. This information was compared with that obtained from a sample of 220 patients--all those who attended the Alcoholism Clinic between July, 1966, and June, 1967. Most of the cirrhotic patients were beer drinkers, as are the majority of Australian alcoholics. Relatively more cirrhotics were habitual excessive drinkers. The cirrhotic patients did not drink more heavily, but they had drunk excessively for longer when their cirrhosis was diagnosed. Cirrhotic women, however, had drunk excessively for a significantly shorter time than cirrhotic men. No difference was found in the incidence of either social isolation or clinical peripheral neuropathy between cirrhotic and alcoholic patients, or between male and female cirrhotics. Cirrhosis was not commoner among the lower socio-economic groups. These findings were interpreted as suggesting that nutrition did not play an important part in the causation of the liver disease. Women appear to be more susceptible than men to cirrhosis of the alcoholic, and unremitting habitual excess more damaging than intermittent alcohol abuse. Some undetermined predisposition must also exist, since the disease is still sporadic even when these factors operate.     

Automatic Implantable Cardioverter Defibrillator/Permanent Pacemaker Interaction: Loss of Pacemaker Capture Following AICD Discharge

A 78-year-old man treated with amiodarone for recurrent ventricular tachycardia, had sequential placement of a bipolar VVI pacemaker and an automatic implantable cardioverter defibrillator (AICD). During defibrillation threshold testing, there was failure to capture of the pacer in the post-shock period. The time of failure to capture appeared energy-related: the greater the energy delivered, the longer the failure to capture. Careful attention will be necessary in constructing combined AICD/pacemaker units.     

Cerebellar Stimulation for Spastic Cerebral Palsy; Preliminary Report; On-going Double Blind Study

To date, June 1, 1986, 33 spastic cerebral palsy (CP) patients have taken part in a double blind study testing the safety and efficacy of chronic cerebellar stimulation (CCS) for reduction of spasticity and improvement in function. Seven U.S. surgical centers involving ten neurosurgeons have implanted the Neurolith 601 cerebellar stimulator supplied by Pacesetter Systems Inc. (Sylmar, CA). A pilot study was run with three patients at Stanford University (Stanford, CA) using taped-on real (strong) and dummy (weak) magnets to control the ON-OFF status. Following the pilot study, a magnetically controllable switch was placed in line between the Neurolith stimulator and the cerebellar lead to allow more reliable switching sequences for the study. The test battery included joint angle measurements (passive and active), motor performance testing, reaction time, hand dynamometry, grooved peg board placement, hand/foot tapping, and rotary pursuit testing. Testing only was done at presurgery. Testing and ON-OFF switching was performed following recovery from surgery and at one, two, and four months. After four months, the switch was left turned ON. Of the 30 patients using the implanted switch, 11 were dropped from the study and seven are still in progress. Of the 11 dropped from the study, four were due to switch problems and three were due to double blind protocol violations, i.e., the participants discovered the stimulus status. The remaining four were removed because of a broken lead, infection, or unrelated medical problems, or refusal to participate after implant. A preliminary analysis indicated that three-quarters of the patients have a demonstrable quantitative improvement during the time the stimulation was "ON." Three patients showed no significant change.     

A Solid-Phase Assay for the Detection of Anti-Sperm Antibodies

PROBLEM: ELISA is an ideal assay method for a large-scale screening of anti-sperm antibodies among a large number of infertile males. However, conventional ELISA with whole spermatozoa needs time-consuming steps of centrifugation. METHOD: A solid-phase assay used for detecting anti-sperm antibodies was established. This assay is suitable not only for detecting circulating anti-sperm antibodies of IgG, IgM, and IgA subclass simultaneously but also for screening hybridomas secreting anti-sperm monoclonal antibodies (mAbs). The microtiter plates, on which solubilized sperm antigens are fixed, can be stored at ? 80°C for up to six months without losing reactivity with anti-sperm antibodies. RESULTS: Using this assay, 53 sera (13 were proven positive and 40 were proven negative for sperm agglutination antibody) were tested. Although the false-negative rate was 0%, the false-positive rate was 32%. One thousand one hundred sixty-five supernatants from hybridomas constructed with splenocytes of mice who were hyperimmunized with human sperm and nonsecreting myeloma cells were tested by this solid-phase assay and two anti-sperm mAb secreting clones were selected and established. CONCLUSIONS: It is recommended that for research work this assay could be used for the first screening of the hybridoma secreting anti-sperm mAb, and for clinical use this assay might be suitable for the first screening of sera of infertile patients. However, conventional bioassays should follow to confirm the biological meaning of the positivity.     

Pharmacokinetic–pharmacodynamic modeling of the hypotensive effect of remifentanil in infants undergoing cranioplasty

Objectives:  Although remifentanil has been used to induce hypotension during surgery in infants, no pharmacokinetic–pharmacodynamic (PKPD) model exists for its quantitative analysis. Our aim was to determine the quantitative relationship between whole blood remifentanil concentration and its hypotensive effect during surgery in infants.
Methods/materials:  We studied seven infants (age 0.3–1 year) who underwent cranioplasty surgery and received remifentanil delivered by a computer-controlled infusion pump during the maintenance of anesthesia. Arterial blood samples to determine remifentanil concentration and mean arterial blood pressure (MAP) measurements were collected. A simultaneous PKPD mixed-effects model was built in NONMEM.
Results:  A total of 77 remifentanil concentrations and 185 MAP measurements were collected. Remifentanil pharmacokinetics was described with a two-compartment model, parameter estimates were 2.99 l·min⁻¹·70 kg⁻¹ for clearance and 16.23 l·70 kg⁻¹ for steady state volume of distribution. Mean baseline MAP was 69.7 mmHg and was decreased as per clinical requirements. A sigmoidal E _max model driven by an effect compartment described the decrease in MAP, with an estimated concentration to decrease MAP by half (EC₅₀) being 17.1 ng·ml⁻¹.
Conclusions:  Remifentanil is effective in causing hypotension. The final model predicts that a steady state remifentanil concentration of 14 ng·ml⁻¹ would typically achieve a 30% decrease in MAP.