THE EFFECT OF o,p''-DDD ON ADRENAL STEROID REPLACEMENT THERAPY REQUIREMENTS

Two patients with adrenal carcinoma treated with 2,2-bis (2-chlorophenyl-4-chlorophenyl)-1,1-dichloroethane (o,p'-DDD) as adjuvant therapy were studied. Both patients developed hypoadrenalism while on o,p'-DDD and apparently adequate dexamethasone replacement therapy. The hypoadrenalism was overcome by increasing steroid replacement therapy. Dexamethasone levels were measured in the serum by radioimmunoassay and shown to be lowered by o,p'-DDD therapy. A study of the absorption and disappearance of dexamethasone from the circulation in response to a (1 mg oral dose indicated that the steroid was absorbed normally but was cleared more rapidly from the circulation of these two patients than from normal controls. This may be due to a change in the type of metabolites excreted. It is suggested that many of the reported side-effects of o,p'-DDD may be due to hypoadrenalism and may be controlled by greatly increasing the steroid replacement dose. The adequacy of corticosteroid replacement therapy may best be assessed by monitoring the levels of ACTH.     

HYPOTHALAMIC HYPOPITUITARISM FOLLOWING CRANIAL IRRADIATION FOR NASOPHARYNGEAL CARCINOMA

Eight patients, one male and seven females, with no pre-existing hypothalamic-pituitary disease, who developed symptoms of hypopituitarism following cranial irradiation for nasopharyngeal carcinoma were studied 5 years or more after radiotherapy. All were GH deficient. Four of the patients with no GH response during insulin tolerance tests (ITT) showed increased GH in response to synthetic human growth hormone releasing factor (GRF-44). Four patients had impaired cortisol responses to ITT, and gradual but diminished cortisol responses to ovine corticotrophin releasing factor (CRF-41). There was no significant difference between mean peak increments in response to ITT and those in response to CRF-41. TSH responses to TRH were delayed in five and absent in two patients; four of these had low free T4 index. Prolactin was raised in all seven women and increased further in response to TRH. Two patients had impaired gonadotrophin responses to LHRH. None of the patients had clinical or biochemical evidence of diabetes insipidus. These data suggest that post-irradiation hypopituitarism in these patients results from radiation damage to the hypothalamus leading to varying degrees of deficiency of the hypothalamic releasing or inhibitory factors.     

Evaluation of the efficacy of a hospital-based asthma education programme in patients of low socioeconomic status in Hong Kong

BACKGROUND: Good asthma control requires optimal medical treatment in conjunction with appropriate self-management. In the West, the effectiveness of patient education on improving self-management has been well documented. However, data amongst Asian populations are lacking. We performed a pilot study to evaluate the efficacy of a hospital based education programme aimed at improving self-management skills and reducing morbidity in a Chinese population with low socioeconomic status and education level. METHODS: Our asthma education programme was a low-cost programme conducted in essence by specialist respiratory nurses. Patients attending our asthma clinic were instructed during a two-hour educational session on the pathophysiology of asthma, its potential triggers, the appropriate use of medications including proper inhaler techniques, and the self-management of their disease. These instructions were reinforced by video sessions at subsequent outpatient clinic attendance when patients' inhaler and peak flow techniques were checked by the same nurses and their self-management plan re-examined by the attending physicians. Asthma knowledge, inhaler technique, FEV1 and peak expiratory flow (PEF), and patients' self-rating of their asthma were determined at baseline, 6 months and 1 year after the intervention. Morbidity was assessed by the numbers of hospitalizations, unscheduled visits to family physicians and accident and emergency department attendance, courses of oral steroid used and days off work or school at baseline and 1 year. RESULTS: Two hundred and thirty patients were recruited for the study, 83% completing the entire assessment period. The group demonstrated significant improvements in lung function: the mean FEV1 +/- SD increased from 63.6 +/- 20.6% of predicted values at baseline to 68.5 +/- 22.3% at 6 months and 68.6 +/- 22.8% at 1 year (P < 0.05), and the mean PEF +/- SD increased from 64.6 +/- 23.0% of predicted values at baseline to 75.4 +/- 27.0% at 6 months and 76.8 +/- 24.5% at 1 year(P < 0.001). There were also significant improvements in inhaler technique (P < 0.01), asthma knowledge (P < 0.001), patients' self-rating of their asthma (P < 0.05), and reductions in the numbers of hospitalizations (P < 0.01), visits to family physicians (P < 0.001) and accident and emergency department attendance (P < 0.001) during the study period. Patients with moderate to severe asthma as defined by an FEV1 of < 80% of predicted values were most likely to benefit from the programme. CONCLUSIONS: We conclude that patient education is likely to be an essential component in the holistic approach to the management of asthma even amongst Asian populations of low socioeconomic status and education level. Further studies using randomised controlled trials are necessary to consolidate our findings.     

Skin Tumorigenic Potential of Crude and Refined Coal Liquids and Analogous Petroleum Products

Skin Tumorigenic Potential of Crude and Refined Coal Liquidsand Analogous Petroleum Products. WITSCHI, H. P., SMITH, L.H., FROME, E. L., PECQUET-GOAD, M. E., GRIEST, W. H., HO. C.-H.,AND GUERIN, M. R. (1987). Fundam. Appl. Toxicol 9, 297–303.The skin tumorigenic potential of seven complex hydrocarbonmixtures was determined: a coal-derived raw blend composed oflight and heavy oils, a low- and high-severity hydrotreatedproduct of that blend, and naphthas and fuel oils from the rawblend or from natural petroleum. Male and female C3H/Bd_f micewere exposed three times per week to each test mixture by dermalapplication of 50 µl of neat, 50, or 25% (w/v) preparations.Room, vehicle, and benzo[a] control groups were run concurrently.The raw blend produced an almost 100% incidence of skin tumorsat all three doses while tuniorigenicity was considerably decreasedby hydrotreating the blend both in terms of incidence and onset.The tumongenicities of the naphthas and fuel oils derived fromthe raw blend or from petroleums were low relative to that ofthe parent mixture. Although tumorigens in the raw blend weremuch reduced by hydrotreatment, tumori genicity of the otheragents did not parallel the content of polycyclic aromatic hydrocarbonsknown to be good tumor initiators.     

Pigmented nail with atypical melanocytic hyperplasia

We report two cases showing black discoloration of the thumb nail which were histologically found to be acral lentiginous melanoma (ALM) in situ. A pigmented subungual lesion is more frequently malignant than benign and it is generally believed that diagnosis of subungual melanoma during the radial-growth phase is very difficult. Our cases are particularly interesting because atypical melanocytic hyperplasia was confined to the epidermis despite the lesion being present for a long time.     

High Density Endocardial Mapping of Shifts in the Site of Earliest Depolarization During Sinus Rhythm and Sinus Tachycardia

BETTS, T.R., et al. : High Density Endocardial Mapping of Shifts in the Site of Earliest Depolarization During Sinus Rhythm and Sinus Tachycardia. Previous mapping studies of sinus rhythm suggest faster rates arise from more cranial sites within the lateral right atrium. In the intact, beating heart, mapping has been limited to epicardial plaques or single endocardial catheters. The present study was designed to examine shifts in the site of the earliest endocardial depolarization during sinus rhythm and sinus tachycardia using high density activation mapping. Noncontact mapping of the right atrium during sinus rhythm was performed on ten anesthetized swine. Recordings were made during sinus rhythm, phenylephrine infusion, and isoproterenol infusion. The hearts were then excised and the histological sinus node identified. The mean minimum and maximum cycle lengths recorded were   355 ± 43   and   717 ± 108 ms   . A median of three (range two to five) sites of earliest endocardial depolarization were documented in each animal. With increasing heart rate the site of earliest endocardial depolarization remained stationary until a sudden shift in a cranial or caudal direction, often to sites beyond the histological sinoatrial node. The endocardial shift was unpredictable with considerable variation between animals; however, faster rates arose from more cranial sites   (r = 0.46, P = 0.023)   . There was no difference in the mean cycle length of sinus rhythm originating from specific positions on the terminal crest   (r = 0.44, P = 0.17)   . Cranial sites displayed a more diffuse pattern of early depolarization than caudal sites. In the porcine heart the relationship between heart rate and site of earliest endocardial depolarization shows considerable variation between individual animals. These findings may have implications for clinical mapping and ablation procedures. (PACE 2003; 26[Pt. I]:874–882)     

Variation of interleukin 8 -251 A>T polymorphism in worldwide populations and intra-ethnic differences in Japanese populations

BACKGROUND: Interleukin-8 (IL8) is a member of the family of chemokines. The IL8 gene has polymorphic variations, and the genotype of IL8 -251 A>T is associated with smoking behavior and cancer progression. METHOD: IL8 -251 A>T polymorphism were investigated in Japanese, from 5 different areas, in Ovambo, Turkish, Mongolian and Korean populations by PCR with confronting 2-pair primers (PCR-CTPP) analysis. RESULTS: A subpopulation analysis of Japan revealed a north-to-south increase in the frequency of the IL8 -251 T allele. Among the 5 groups, the Japanese showed the highest frequency of mutant allele followed by the Turks. The distribution pattern in the Japanese was different from those of Mongolians and Koreans. In the Ovambo population, no mutant allele homozygote subject was found and the frequency of mutant alleles was the lowest, similar to that in Gambians. CONCLUSION: The present study is the first to demonstrate the Japan population inter-prefecture differences in IL8 -251 A>T polymorphism as well as a certain genetic heterogeneity in the worldwide distribution of IL8 -251 A>T polymorphism. The distribution results may help define the true significance of IL8 -251 A>T polymorphism as a marker for smoking behavior in populations worldwide.