A case of small cell carcinoma of the lung associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome]

A 51-year-old male who showed severe ataxia, dysarthria, bilateral blepharoptosis, diplopia and nystagmus with the subacute onset was reported. The chest roentgenogram and CT scan revealed mass lesions at the hilus of the left lung. The tumor markers, NSE and ProGRP, were elevated; 12.8 ng/ml (< or = 10) and 140.7 pg/ml (< or = 46), respectively. The biopsy was performed surgically and the small cell carcinoma of the lung was confirmed pathologically. His cerebellar symptoms were considered to be caused by the paraneoplastc cerebellar degeneration. However, the blepharoptosis was peculiar. The electrophysiological studies were carried out The muscle strength test of the right APB muscle was 5. But the supramaximum stimulation of the right median nerve evoked only 2.0 mV of CMAP of the right APB muscle. The repetitive stimulation tests of the same nerve showed that 3 Hz stimulation resulted in 42% waning but 20 Hz stimulation evoked no waxing. The post-exercise test of the right APB muscle showed 73% increase of the CMAP. These findings indicated that he also suffered from Lambert-Eaton myasthenic syndrome. The titer of the antibody against the P/Q type voltage-gated calcium channel (VGCC) was remarkably elevated, 1,920 pM. None of the following antibodies were detected ; they included antibodies against acetylcholine receptor, Hu, Yo, Ri, Ma-2, CRMP-5, amphiphysin and glutamic acid dehydrogenase. The small cell carcinoma was treated with the combination of irinotecan hydrochloride and cisplatin, leading to the reduction of the mass lesions and the tumor markers. His cerebellar symptoms improved slightly but his blepharoptosis was unchanged. The titer of antibody against the P/Q type VGCC reduced remarkably to 451.8 pM. We reviewed reported cases associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome and discussed the relation between the paraneoplastic syndromes and autoantibodies.     

Validity and reliability of the Japanese version of the Neuropsychiatric Inventory Caregiver Distress Scale (NPI D) and the Neuropsychiatric Inventory Brief Questionnaire Form (NPI-Q)]

OBJECTIVE: Neuropsychiatric disturbances are common and burdensome symptoms of dementia. Assessment and measurement of neuropsychiatric disturbances are indispensable to the management of patients with dementia. Neuropsychiatric Inventory (NPI) is a comprehensive assessment tool that evaluates psychiatric symptoms in dementia. We translated the NPI-Caregiver Distress Scale part of NPI (NPI-D) and NPI-Brief Questionnaire Form (NPI-Q) into Japanese and examined their validity and reliability. SUBJECTS AND METHODS: The subjects were 152 demented patients and the caregivers who lived with them. These patients consisted of 76 women and 76 men; their mean age was 73.9 +/- 7.8 (S.D.; range: 49 to 93) years. Their caregivers consisted of 46 men and 106 women; their mean age was 65.0 +/- 11.4 (S.D.; range: 35 to 90) years. The Mini-Mental State Examination (MMSE) was conducted with all patients and NPI-Q, NPI, NPI-D, and the Zarit caregiver burden interview (ZBI) were conducted with all caregivers. We examined validity of NPI-D by comparing its score with the MMSE and ZBI scores, and the validity of NPI-Q by comparing its score with the NPI and NPI-D scores. In order to evaluate test-retest reliability, NPI-D was re-adopted to 30 randomly selected caregivers by a different examiner one month later and NPI-Q was re-executed by 27 randomly selected caregivers one day later. RESULTS: Total NPI-D score was significantly correlated with ZBI (rs = 0.59, p < 0.01). Test-retest reliability of NPI-D was adequate (ri = 0.47, p < 0.01). Total NPI-Q severity score and distress score were strongly correlated with NPI (r = 0.77, p < 0.01) and NPI-D (r = 0.80, p < 0.01) scores, respectively. Test-retest reliability of the scores of NPI-Q was acceptably high (the severity score; ri = 0.81, p < 0.01, the distress score; ri = 0.80, p < 0.01). CONCLUSION: The Japanese version of NPI-D and NPI-Q demonstrated sufficient validity and reliability as well as the original version of them. These are useful tools for evaluating psychiatric symptoms in demented patients and their caregivers' distress attributable to these symptoms.     

Correlation between inflammatory cellular responses and chemotactic activity in bronchoalveolar lavage fluid following intratracheal instillation of nickel sulfate in rats

In a preceding study, we reported that the numbers of macrophages and polymorphonuclear leukocytes (PMN) were increased in bronchoalveolar lavage fluid (BALF) following the intratracheal instillation of nickel sulfate (NiSO₄) in rats. In the present study, BALF chemotactic activities for both macrophages and PMN were measured to investigate if the increases of these inflammatory cells in BALF depend on increases in chemotactic activities in epithelial lining fluid (ELF) of the lung. Both the number of PMN and the PMN chemotactic activity peaked at 2 days post-instillation and they were significantly correlated. However, the PMN chemotactic activity was inversely correlated with concentration of leukotriene B₄ (LTB₄), a well-known chemotaxin. Although PMN were not observed in control BALF, LTB₄ concentration in the control ELF (ca. 5×10^–7 M) was estimated to have a potential to attract PMN chemotactically through a membrane in in vitro migration assay. These results suggest that the presence of LTB₄ in ELF itself does not trigger transpulmonary PMN infiltration. The rat BALF were fractionated by high performance liquid chromatography (HPLC), and PMN chemotactic activity of each fraction was measured. The elution profiles of PMN chemotactic activity showed that there were at least two different chemotaxins in BALF obtained from the NiSO₄-exposed rats. Macrophage chemotactic activity in BALF also peaked at 2 days post-instillation. However, the number of macrophages was not significantly correlated with the chemotactic activity for macrophage in BALF. The HPLC study showed that the macrophage chemotactic substance in the BALF obtained from NiSO₄-exposed rats was different from complement fragment (C5a) and its MW was estimated to be 10 – 12 kD. Received: 1 December 1993/Accepted: 16 March 1994     

Genetic alteration in carcinoid tumors of the lung.

Surgically resected specimens of 13 carcinoid tumors of the lung including nine typical carcinoids and four atypical carcinoids, and eight salivary gland type carcinomas (six mucoepidermoid carcinomas and two adenoid cystic carcinomas) were analyzed regarding p53 expression, loss of heterozygosity (LOH) in chromosome 3p, 9p, and K-ras mutation. The overexpression of p53 was identified in four atypical carcinoid tumors, one mucoepidermoid carcinoma, and one adenoid cystic carcinoma, however, none of typical carcinoids showed p53 immunoreactivity. LOH in 3p14 was demonstrated in three of seven informative cases in all tumors. LOH in 9p was demonstrated in two of five informative cases in all tumors. Two of three cases with LOH at 3p14 had a poor prognosis, one of which also had LOH at 9p. No mutation of the K-ras gene was observed in any of these tumors. These data thus indicate that p53 overexpression might distinguish atypical carcinoid tumors from typical tumors and might therefore be useful as an adjunct modality in the differential diagnosis of pulmonary carcinoid tumors. The presence of LOH at 3p14 or 9p may thus help to identify lung cancer patients with a poor prognosis.     

Preliminary evaluation of the processes of changing to a low-fat diet

The purpose of the present paper is to identify the processesof changing dietary fat consumption using Prochaska's transtheoreticalmodel. This model assigns individuals into a series of stages,emphasizing the cognitive, social and behavioral steps of change.At each of the stages an individual focuses on different processes,or coping strategies, to enable movement to the next stage.Dietary process items were created by a multidisciplinary teamusing the smoking processes as a model. These items were subjectedto a Q-sort and piloted in convenience samples. The processitems were distributed with staging questionnaires to 720 membersof an outdoor folk music festival audience. The final groupof 121 process items was subjected to exploratory factor analysisof principle components with varimax rotation. Eight independentfactors emerged during this factor analysis. The processes measuredby the final 60-item questionnaire relate to the stages of changein the hypothesized manner. Applications of this model to interventionsettings seem possible.     

Human cellular immune response to Giardia lamblia

Summary Human peripheral blood mononuclear cells (PBMC) from two individuals experimentally and one naturally infected withGiardia lamblia responded strongly (in anin vitro lymphocyte proliferation assay) to both heterologous and homologous (parasite origin)G. lamblia antigen stimuli. Proliferative responses to specific antigens as determined by T-cell blotting were due toGiardia T-cell epitopes mostly present in antigens lower than M_r 85,000 and 31,000 in isolates PM and GS/M-H7, respectively. Additionally, Il-2 production of PBMC respective to T lymphocyte subsets under antigen stimulation were determined in one selected patient. Proliferative and lymphokine responses could be associated with CD4⁺ PBMC depleted of CD8⁺ T cells and not with PBMC depleted of CD4⁺ T cells. These preliminary results suggest the initiation of larger studies addressing questions of cell-mediated immune response and the role of lymphokines in human giardiasis.

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Zelluläre Immunreaktion gegen Giardia lamblia beim Menschen

Zusammenfassung Periphere Blutmonozyten von zwei Personen mit einer experimentell und einer mit einer natürlich erworbenenGiardia lamblia-Infektion zeigten eine ausgeprägte lymphoproliferative Antwort nachIn-vitro-Stimulation mit Parasitenantigen, das sowohl aus homologen als auch heterologen Parasitenisolaten gewonnen worden war. Eine T-Zell-Blot- Analyse der lymphoproliferativen Immunantwort bezüglich der nach Molekulargewicht aufgetrenntenGiardia-Antigenkomponenten zeigte, daß das Spektrum derGiardia-Antigene mit T-Zell-Epitopen im M_r-Bereich von < 85'000 für das PM-1-Isolat und < 31'000 für das GS/M-H7-Isolat lagen. Bei einem der Patienten wurden Lymphozyten nach antigen-spezifischerIn-vitro-Proliferation auf ihre Lymphozytensubpopulationen und deren Fähigkeit zur Il-2-Produktion untersucht. Eine lymphoproliferative Antwort, verkoppelt mit einer Il-2-Produktion, war nur bei CD4⁺ Lymphozyten (nach entsprechender Eliminierung von CD8⁺ Lymphozyten) und nicht bei CD8⁺ Lymphozyten (nach entsprechender Eliminierung von CD4⁺ Lymphozyten) nachweisbar.

     

Childhood precursors of age at first intercourse for females

Age at first intercourse for a sample of adult white women using variables measured during childhood is predicted. Childhood predictors were measured at birth, and ages 5 and 9–11, using existing public-use data on the women. Median age at first intercourse for the sample was 17.5 years. Early family predictors, early developmental characteristics, and temperamental characteristics during childhood together could predict about a fourth of the variance in age at first intercourse. The strongest predictors were motor skills and nightmares at age 5, church attendance with family at age 9, and domineering and mature personality at age 9.This research was supported by grants R01-HD23454 and P30-HD05798 from the National Institute of Child Health and Human Development. An earlier version of this paper was presented at the annual meetings of the Population Association of America, Denver, Colorado, April 30–May 2, 1992.     

Autoantibodies in scleroderma and tightskin mice

There is much evidence to suggest that scleroderma in human patients is caused by a fundamental defect in the immune system. In tightskin mice, the scleroderma syndrome is associated with autoimmunity, particularly autoantibodies interacting with scleroderma target antigens.