An active liver transplant programme for hepatocellular carcinoma in cirrhotic patients: is it justified?

Even at an early stage, hepatocellular carcinoma (HCC) in patients with cirrhosis is often deemed unresectable because of limited liver reserve. In these circumstances, liver transplantation (LTx) offers some hope for palliation or cure. The results of LTx for selected cirrhotic patients with HCC were analysed. The outcomes were compared with those of patients who underwent LTx for other forms of hepatic malignancy and those who underwent LTx for non-malignant conditions. Four hundred and eighty LTx were performed in 441 patients between January 1986 and December 1998. Twenty-eight LTx recipients (25 males, 3 females) of mean age 51 (14 63) yr had cirrhosis and HCC. Twenty-seven patients had underlying predisposing conditions (11 had hepatitis B, 10 had hepatitis C, 2 had hepatitis B and C, 1 had haemochromatosis, 1 had autoimmune hepatitis, 1 had alcoholic cirrhosis and 1 had alpha-1 antitrypsin deficiency). In 22 patients, HCC was diagnosed pre-LTx, and in 6 patients, the cancers were discovered incidentally. The average tumour size and number were 2.8 (0.4-11.5) cm and 1.3 (1-4), respectively. Two patients with known HCC died during and shortly after the LTx operation. Of the other patients, 3 died; 1 died of HCC recurrence 18 months post-LTx, 1 died of graft failure from recurrent hepatitis C and 1 died of fungal sepsis. Twenty-three (82%) patients survived to 22.5 (0.5-96) months post-LTx without HCC recurrence and with 1- and 3-yr actuarial patient survival rates of 87 and 76%, respectively. Equivalent survival rates of patients who underwent LTx for other malignancies (n = 11) were 82 and 46% (p = NS), and for those who underwent LTx for benign causes (n = 402), they were 77 and 73% (p = NS). All 15 patients with known HCC, who met the selection criteria now in use, survived. LTx can result in prolonged. cancer-free survival in a good proportion of patients with cirrhosis and HCC, particularly when the cancers are incidental, or when diagnosed pre-LTx, conforming to established selection criteria. An active LTx programme for this group of patients is justified.     

Analysis of Voice Changes After Thyroplasty Using Linear Predictive Coding

Objective measurement of vocal quality is difficult in patients with severe voice disorders. Improved success has been reported using a modeling technique known as linear predictive coding. This technique uses an inverse filter to estimate a glottic excitation signal. The pitch amplitude is defined as the height of the first peak of the autocorrelation of the glottic excitation signal. In this study linear predictive coding was used to analyze voice disorders in patients with vocal fold immobility. Voice recordings were made in 16 patients undergoing vocal fold medialization and 10 patients who had no surgical procedure between measurements. The voice quality was rated by three speech pathologists. Five acoustic parameters were calculated from the samples. The best agreement with the listeners' perceptual analysis was achieved using the pitch amplitude. Both pitch amplitude and the perceptual ratings of voice quality improved in patients undergoing vocal fold medialization. Therefore the linear model of speech production and inverse filtering are useful in measuring vocal quality in patients with vocal fold immobility.     

Rising incidence of type 1 diabetes in Scottish children, 1984-93. The Scottish Study Group for the Care of Young Diabetics

OBJECTIVES: To calculate the incidence of type 1 diabetes in Scottish children aged less than 15 years between 1984 and 1993; to examine changes in incidence; and to calculate the prevalence of diabetes at the end of this period. DESIGN: Three data sources were used to construct the Scottish Study Group for the Care of Young Diabetics register: active reporting of all new cases; reports from the Scottish Morbidity Register 1; and local registers. SUBJECTS: All children resident in Scotland diagnosed with primary insulin dependent diabetes mellitus when less than 15 years of age between 1984 and 1993. MAIN OUTCOME MEASURES: Annual incidence and prevalence rate for Scotland; time trend in incidence over the 10 years; differences in incidence between the three different age groups; and completeness of the register. RESULTS: The average annual incidence for Scotland was 23.9/100,000 children. The prevalence rate was 1.5/1000 in 1993. A total of 2326 cases was identified from the three sources. Capture-recapture analysis suggests a case ascertainment of 98.6%. The annual incidence rates increased at a rate of 2% each year (rate ratio = 1.02, 95% confidence interval (CI) 1.01 to 1.03). The incidence was higher in boys than girls (rate ratio = 1.08, 95% CI 1.00 to 1.18), and the incidence rates increased with age: 15.3/100,000/year for age 0-4 years, 24.4/ 100,000/year for age 5-9 years, and 31.9/ 100,000/year for age 10-14 years. CONCLUSIONS: The incidence of type 1 diabetes in Scotland is increasing and the prevalence is relatively high. These findings have important implications for health service resource allocation. The Scottish Study Group for the Care of Young Diabetics' register provides a base for monitoring and research.     

Randomised controlled trial of advice on an egg exclusion diet in young children with atopic eczema and sensitivity to eggs

Background: The role of exclusion diets in the management of atopic eczema in young children is uncertain. This randomised controlled trial evaluates the effect of excluding egg from the diet in young children with atopic eczema and sensitivity to eggs. Fifty-five such children were randomised either to a 4-week regimen, in which mothers were given general advice on care of eczema and additional specific advice from a dietician about an egg exclusion diet (diet group), or to a control group in which general advice only was given. Both groups continued conventional topical treatment. Disease activity was assessed by estimates of the surface area affected by eczema and by an arbitrary severity score. Possible egg sensitivity was identified by RAST before randomisation and after the trial by double-blind placebo-controlled egg challenge. Results: The mean reduction in surface area affected by eczema was significantly greater (p = 0.02) in the group receiving dietary advice (from 19.6% to 10.9% area affected) than in the control group (from 21.9% to 18.9%). A significant improvement also occurred in severity score (p=0.04): from 33.9 to 24.0 units for the diet group compared with a decrease from 36.7 to 33.5 in the control group. The study suggests that advice on the dietary exclusion of eggs is useful as part of the overall management of young children with atopic eczema and sensitivity to eggs.     

Reflex sympathetic dystrophy in a 12-year-old twin with comorbid conversion disorder in both twins

A case of reflex sympathetic dystrophy is presented in a 12-year-old girl with comorbid conversion disorder. Her identical twin also had a conversion disorder. This is the first reported case of coexistence of reflex sympathetic dystrophy and conversion disorder. It is important for clinicians to be aware that these conditions may coexist since the presentation of symptoms differ, even though there are shared features of treatment.     

Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz

The present study investigated the effects of dietary oltipraz on cigarette smoke-related lipophilic DNA adduct formation. Female Sprague- Dawley rats were exposed daily to sidestream cigarette smoke in a whole- body exposure chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained on control diet while another group received the same diet supplemented with either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz, starting 1 week prior to initiation of smoke exposure until the end of the experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated 32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5 predominated in both the lung and the heart while adduct nos 3 and 2 predominated in the trachea and bladder, respectively. Quantitative analysis revealed that the total adduct level was the highest in lungs (270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48 adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides) and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraz treatment reduced the adduct levels in lungs and bladder by >60%, while the reduction in lungs in the low-dose group was approximately 35%. In trachea, the effect of low and high dietary oltipraz on smoke DNA adduction was equivocal, while smoke-related DNA adducts in the heart were minimally inhibited by high-dose oltipraz. In a repeat experiment that employed a 3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to inhibit the formation of DNA adducts in rat lungs and trachea by 80 and 65%, respectively. These data clearly demonstrate a high efficacy of oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts in the target tissues.      

Contact area affects frequency-dependent responses to vibration in the peripheral vascular and sensorineural systems

Repetitive exposure to hand-transmitted vibration is associated with development of peripheral vascular and sensorineural dysfunctions. These disorders and symptoms associated with it are referred to as hand-arm vibration syndrome (HAVS). Although the symptoms of the disorder have been well characterized, the etiology and contribution of various exposure factors to development of the dysfunctions are not well understood. Previous studies performed using a rat-tail model of vibration demonstrated that vascular and peripheral nervous system adverse effects of vibration are frequency-dependent, with vibration frequencies at or near the resonant frequency producing the most severe injury. However, in these investigations, the amplitude of the exposed tissue was greater than amplitude typically noted in human fingers. To determine how contact with vibrating source and amplitude of the biodynamic response of the tissue affects the risk of injury occurring, this study compared the influence of frequency using different levels of restraint to assess how maintaining contact of the tail with vibrating source affects the transmission of vibration. Data demonstrated that for the most part, increasing the contact of the tail with the platform by restraining it with additional straps resulted in an enhancement in transmission of vibration signal and elevation in factors associated with vascular and peripheral nerve injury. In addition, there were also frequency-dependent effects, with exposure at 250 Hz generating greater effects than vibration at 62.5 Hz. These observations are consistent with studies in humans demonstrating that greater contact and exposure to frequencies near the resonant frequency pose the highest risk for generating peripheral vascular and sensorineural dysfunction.     

From the Cover: Loss of phosphatidylinositol 4-kinase 2α activity causes late onset degeneration of spinal cord axons

Phosphoinositide (PI) lipids are intracellular membrane signaling intermediates and effectors produced by localized PI kinase and phosphatase activities. Although many signaling roles of PI kinases have been identified in cultured cell lines, transgenic animal studies have produced unexpected insight into the in vivo functions of specific PI 3- and 5-kinases, but no mammalian PI 4-kinase (PI4K) knockout has previously been reported. Prior studies using cultured cells implicated the PI4K2α isozyme in diverse functions, including receptor signaling, ion channel regulation, endosomal trafficking, and regulated secretion. We now show that despite these important functions, mice lacking PI4K2α kinase activity initially appear normal. However, adult Pi4k2a^GT/GT animals develop a progressive neurological disease characterized by tremor, limb weakness, urinary incontinence, and premature mortality. Histological analysis of aged Pi4k2a^GT/GT animals revealed lipofuscin-like deposition and gliosis in the cerebellum, and loss of Purkinje cells. Peripheral nerves are essentially normal, but massive axonal degeneration was found in the spinal cord in both ascending and descending tracts. These results reveal a previously undescribed role for aberrant PI signaling in neurological disease that resembles autosomal recessive hereditary spastic paraplegia.     

Increased susceptibility of peripheral mononuclear cells of leukemic patients to HTLV-I infection in vitro

Peripheral mononuclear cells (MNC) collected from 12 healthy donors and 44 leukemic patients at various stages of the disease were tested for natural killer (NK) activity and for their susceptibility to HTLV-I infection in vitro, measured in terms of percentage of p19 positive cells. MNC from leukemic donors at any stage of leukemia (ie, onset or relapse, ON/REL; complete remission or off-therapy, CR/OT donors) were highly susceptible to HTLV-I infection. This was true for acute leukemias of lymphoblastic (ALL) or nonlymphoblastic (ANLL) type. MNC of ON/REL patients were more susceptible to HTLV-I than those of CR/OT donors. In addition, leukemic blasts were more rapidly infected (ie, within five to seven days) than the HTLV-I-susceptible normal cord- blood lymphocytes. However, the presence of circulating blasts was not essential to virus susceptibility, since CR/OT MNC, presumably free of leukemic blasts, were still more susceptible to HTLV-I than normal cells. Basal NK function of MNC from leukemic patients was significantly lower than that detectable in healthy controls. However, no correlation was found between susceptibility to HTLV-I infection and NK activity.