The morbidity, time course and predictive factors for persistent post-thoracotomy pain.

After thoracotomy, patients often suffer from a persistent pain syndrome called post-thoracotomy pain. To elucidate morbidity, time course, and predictive factors for this syndrome, we analyzed follow-up data for 85 post-thoracotomy patients. We used a four-point scale to assess pain: none, slight, moderate and severe. Of 85 patients, 50 reported pain (39 slight, 11 moderate) one day after surgery. A year after surgery, the patients were polled using a simple questionnaire received by the mail. Sixty patients reported persistent pain (34 slight, 14 moderate, 12 severe) a month after surgery, and 35 patients reported persistent pain (33 slight, two moderate) around the time of the poll (1 year after surgery). Although pain deterioration was observed in 40% (34/85) of patients during month 1 after surgery, pain alleviation was seen in 48% (41/85) of patients during months 2-12. Stepwise regression analysis revealed that female gender and pain at postoperative day 1 were predictive for persistent pain both 1 month and 1 year after thoracotomy. Among 35 patients with persistent pain 1 year after surgery, 24 cases reported paresthesia-dysesthesia, and 14 cases reported hypoesthesia. The present data thus suggests that persistent pain is common and often severe 1 month after surgery but is alleviated after 1 year. Clinical time course and symptoms indicate that nerve impairment rather than simple nociceptive impact may be involved in this syndrome.

Mutations producing premature termination of translation and an amino acid substitution in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis associated with parkinsonism.

OBJECTIVES: Mutational analysis of the sterol 27-hydroxylase (CYP27) gene was performed on three patients from two Japanese families who had cerebrotendinous xanthomatosis (CTX) associated with parkinsonism. METHODS: Clinical evaluations, brain MRI studies, and laboratory analyses were completed on the three patients. The CYP27 gene was analysed for mutations by PCR amplification of gene segments followed by direct sequencing. RESULTS: Two different, homozygous mutations were identified in these families. One is a novel transition, substituting T for G at Glu162 (GAG) resulting in a stop codon (TAG). The other is also a transition, substituting T for C at Arg441 (CGG) resulting in Trp (TGG). The second is located in two amino acids ahead of the heme ligand binding site (Cys443) of the protein likely rendering it non-functional. It is the most common CTX mutation in Japanese patients. CONCLUSIONS: CTX with parkinsonism is caused by mutations with a severe impact on enzyme function. The two mutations described here are likely to cause loss of function because they are chain terminating or affect an essential site in the protein.

Missense and nonsense mutations in the lysosomal alpha-mannosidase gene (MANB) in severe and mild forms of alpha-mannosidosis.

alpha-Mannosidosis is an autosomal recessive lysosomal-storage disorder caused by a deficiency of lysosomal alpha-mannosidase activity. This disease shows a wide range of clinical phenotypes, from a severe, infantile form (type I), which is fatal at <3-8 years of age, to a less severe, late-onset form (type II), which ultimately may involve hearing loss, coarse face, mental retardation, and hepatosplenomegaly. To elucidate the molecular mechanism underlying this disease in both types of patients, we have used PCR, followed by either SSCP analysis or direct sequencing, to analyze the 24 exons and intron/exon boundaries of the alpha-mannosidase gene (MANB) from five patients. Two amino acid substitutions-H72L and R750W, in exons 2 and 18, respectively-and two nonsense mutations-Q639X and R760X, in exons 15 and 19, respectively-were identified in four type II patients. One amino acid substitution, P356R, was identified in exon 8 from a type I patient. This patient and three of the type II patients were homozygous for their mutations (H72L, P356R, R750W, and R760X) and one type II patient was heterozygous for the Q639X and R750W mutations. Transfection experiments of COS 7 cells, using the alpha-mannosidase cDNA containing one of the missense mutations-H72L, P356R, or R750W-revealed that each of these mutations dramatically reduces the enzymatic activity of alpha-mannosidase. These data demonstrate that widely heterogeneous missense or nonsense mutations of the MANB gene are the molecular basis underlying alpha-mannosidosis.

Characterization of the human MANB gene encoding lysosomal alpha-D-mannosidase.

Genomic clones of human MANB gene encoding the lysosomal enzyme, alpha-mannosidase, have been isolated, sequenced and analyzed. The human MANB gene spans approximately 22 kb and consists of 24 exons. The 5' flanking region of the gene shows a high G+C content and has two Sp1 and three AP-2 sites. Promoter analysis using deletion constructs of the 5' flanking region fused to the bacterial CAT gene showed that 150 bp of 5' sequence could drive the expression of MANB in COS 7 cells. Determination of the sequence of the 5' end of the alpha-mannosidase mRNA by 5' RACE protocol showed that transcription is initiated from a cluster of sites centered -28 and -20 bp from the first in-frame ATG. These data demonstrate that, like other lysosomal enzyme genes such as those for beta-glucuronidase or beta-hexosaminidase, the human MANB gene is controlled by a short 5' flanking sequence located near the initiation codon.

[Statistical analysis of trophoblastic disease in Kanagawa prefecture].

Two thousand one hundred and thirty-five cases of trophoblastic disease were registered in Kanagawa Prefecture in 7 years (from 1978 to 1984). The incidence of trophoblastic diseases, hydatidiform mole, partial mole, invasive mole, choriocarcinoma and persistent trophoblastic disease (PTD) was 3.22, 1.67, 1.20, 0.07, 0.06 and 0.20, respectively, per 1,000 live births. The incidence was constant for 7 years, and did not differ significantly from that of 16 prefectures in Japan. In Kanagawa, the incidence of hydatidiform mole was less and that of partial mole was more than those in the 16 prefectures. The incidence of invasive mole and choriocarcinoma was lower and that of PTD was higher than those in the 16 prefectures. Total incidence of invasive mole, choriocarcinoma and PTD was higher in the western part of Japan, and lower in the eastern and northern parts. Kanagawa Prefecture is between these two regions. The distribution by age of hydatidiform mole was high in 25-29 y.o. and over 40 y.o. The distribution by age of partial mole tended to be similar to that of hydatidiform mole, but less remarkable. The distribution by age of invasive mole and choriocarcinoma had 2 peaks of 30-34 y.o. and 45-49 y.o. The distribution by age of PTD was between that of hydatidiform mole and choriocarcinoma.

The rise in medical care expenditures in Japan, trends in disease patterns: 1977-81.

In Japan, the nationwide cost of medical care is increasing rapidly. Analysis of data from the Japanese health insurance system shows that costs are not rising for all diagnoses and that it is diseases requiring hospitalization and expensive medical treatments that have been responsible for the rising cost of medical care.