Diphenhydramine dependence through deep intramuscular injection resulting in myonecrosis and prolonged QT interval.

WHAT IS KNOWN AND OBJECTIVE: Diphenhydramine (DPH) is a first-generation antihistamine, which is useful in treating allergic reaction, and is usually considered innocuous. We describe a retired nurse with history of depression, who began to develop drug-seeking behaviour after her first receiving of an intramuscular (IM) DPH injection due to urticaria. CASE SUMMARY: The 49-year-old patient had developed IM DPH dependence within 4 months. She needed to receive psychiatric inpatient treatment because of depressive mood, serious myonecrosis over injected sites, and prolongation of QT interval. WHAT IS NEW AND CONCLUSION: This is the first reported case of DPH dependence through the IM route. Second-generation antihistamines might be better choices for patients with psychiatric illness by reason of their lower effects on central nervous system and lower risk of abuse.

Microinjection of mouse eggs.

A technique has been developed for injecting known amounts of liquids into fertilized one-celled mouse eggs by use of a calibrated ocular micrometer superimposed on the terminal regions of the injection pipette. From 128 pronuclear eggs, each injected with 180 or 770 cubic microns of bovine gamma globulin at a concentration of 25 milligrams per milliliter in citrate-Locke's solution and then transferred to the oviducts of pregnant foster mothers, 18 living fetuses developed; from 74 eggs, each injected with 2730 cubic microns, 5 fetuses survived. The living fetuses that developed from the injected eggs were smaller than normal in 6 of 23 surviving experimental fetuses as contrasted to only 1 of 19 control fetuses.

Tuberculosis outcomes in Taipei: factors associated with treatment interruption for 2 months and death.

SETTING: All individuals reported as being treated for pulmonary tuberculosis (PTB) among citizens of Taipei City, Taiwan, in 2003. OBJECTIVES: To investigate risk factors associated with treatment interruption for at least 2 consecutive months and death. DESIGN: The outcome of PTB cases was determined by consulting medical charts. RESULTS: Of 1127 PTB patients registered, 824 (73.1%) were successfully treated, 189 (16.8%) died, 65 (5.8%) interrupted treatment, 17 (1.5%) were still on treatment 15 months after commencing treatment and 32 (2.8%) failed. The only significant factor associated with treatment interruption was visits to other health facilities after commencing tuberculosis (TB) treatment. TB patients had a standardised mortality ratio of 8.7 (95%CI 7.5-10.0). Factors significantly associated with death were age (adjusted hazard ratio [adjHR] 1.06. 95%CI 1.05-1.08), sputum culture not performed/unknown (adjHR 2.07, 95%CI 1.47-2.92), and comorbidity with respiratory disease (adjHR 1.68, 95%CI 1.24-2.27), infectious disease (adjHR 2.80, 95%CI 2.07-3.78), renal disease (adjHR 2.58, 95%CI 1.82-3.66) or cancer (adjHR 3.31, 95%CI 2.35-4.65), compared with other patients. CONCLUSION: Visits to other health facilities were associated with interruption of treatment for at least 2 months. A high proportion of deaths was due to old age and comorbidity.

Factors associated with a clinician's decision to stop anti-tuberculosis treatment before completion.

OBJECTIVES: To investigate the diagnosis of pulmonary tuberculosis (PTB) and factors associated with a clinician's decision to stop anti-tuberculosis treatment before completion. DESIGN: The medical charts of all citizens of Taipei City, Taiwan, reported to have received treatment for PTB in 2003 were investigated. RESULTS: Of 1126 PTB patients, 512 (45.5%) started treatment immediately based solely on chest X-ray (CXR) findings; treatment for 214 (19.0%) was based on a positive sputum smear for acid-fast bacilli, for 261 (23.2%) it was based on other findings and for 139 (12.3%) it was based on a positive mycobacterial culture. Of the 1126 PTB patients, 156 (13.9%) had their diagnosis of TB changed by a clinician. Multivariate analysis shows that patients whose diagnosis was based on CXR or other findings, female patients, patients who interrupted treatment for 2 months, patients who continued care at other health facilities (transfer) and patients with lung cancer were significantly more likely to have their diagnosis changed than other groups. CONCLUSION: A substantial proportion of patients were prescribed anti-tuberculosis treatment based on CXR findings alone, and a considerable proportion were advised to stop treatment before completing a full course, findings that require the immediate attention of Taiwan's National Tuberculosis Programme.

Accuracy of classification of notified tuberculosis cases in Taiwan.

SETTING: Tuberculosis (TB) suspects and cases reported in 2003 in Taiwan. OBJECTIVES: To evaluate the accuracy of the classification of notified TB cases in Taiwan. DESIGN: A list of all TB cases reported in 2003 in Taiwan was obtained from the Taiwan Center for Disease Control, along with their classification. TB cases residing in Taipei City were investigated by consulting their medical charts. RESULTS: Of 1,973 patients, 782 (39.6%) were bacteriologically confirmed, 1,024 (52%) were not bacteriologically confirmed (indeterminate) and 167 (9%) were not TB cases (in whom non-tuberculosis mycobacteria [NTM] was isolated). Of the 1,973 cases, 1,716 (87%) had been treated with anti-tuberculosis drugs, while 257 (13%) had not been treated. Of the 782 bacteriologically confirmed cases, 68 (8.7%) were misclassified as non-notifiable (32 [4.1%] had their diagnosis changed by a clinician and 36 [4.6%] by administrative coding). Of the 167 cases in whom NTM were isolated, 72 (43.1%) were misclassified as TB cases. Of the 257 untreated suspects, 31 (12.1%) did not have any evidence of TB (20 indeterminate and 11 NTM cases) and were questionably classified as newly diagnosed cases. CONCLUSION: There was substantial misclassification of notified TB cases in Taiwan.

Transgenes expressing the Wnt-1 and int-2 proto-oncogenes cooperate during mammary carcinogenesis in doubly transgenic mice.

The Wnt-1 and int-2 proto-oncogenes are transcriptionally activated by mouse mammary tumor virus insertion mutations in virus-induced tumors and encode secretory glycoproteins. To determine whether these two genes can cooperate during carcinogenesis, we have crossed two previously characterized lines of transgenic mice to obtain bitransgenic animals carrying both Wnt-1 and int-2 transgenes under the control of the mouse mammary tumor virus long terminal repeat. Mammary carcinomas appear earlier and with higher frequency in the bitransgenic animals, especially the males, than in either parental line. Nearly all bitransgenic males develop mammary neoplasms within 8 months of birth, whereas only 15% of Wnt-1 transgenic males and none of the int-2 transgenic males have tumors. In virgin bitransgenic females, tumors occur approximately 2 months earlier than in their Wnt-1 transgenic siblings; int-2 transgenic females rarely exhibit tumors. Preneoplastic glands from the bitransgenic animals of either sex demonstrate pronounced epithelial hyperplasia similar to that seen in Wnt-1 transgenic virgin females and males, and both transgenes are expressed in the hyperplastic glands and mammary tumors. RNA from the int-2 transgene is more abundant in mammary glands from bitransgenic animals than from int-2 transgenic animals; the increase is associated with high levels of RNA specific for keratin genes 14 and 18, suggesting that Wnt-1-induced epithelial hyperplasia is responsible for the observed increase in expression of the int-2 transgene.

Role of endocrine, autocrine, and paracrine interactions in the development of mammary hyperplasia in Wnt-1 transgenic mice.

The Wnt-1 proto-oncogene is transcriptionally activated by mouse mammary tumor virus in mouse mammary tumor virus-induced tumors. Previous studies using transgenic mice showed that Wnt-1 expression in mammary gland causes alveolar hyperplasias which resemble mammary glands of pregnant mice. To understand the role of mammogenic hormones in the genesis of these hyperplasias, we examined the development of these glands before puberty in young transgenic mice and the effects of ovariectomy and adrenalectomy on the growth and morphology of Wnt-1 mammary hyperplasia. Mammary glands of Wnt-1 transgenic females showed hyperplastic morphology as early as 1 week after birth. The normal structure of the uterus of the adult Wnt-1 virgin mouse indicated that the circulating levels of ovarian hormones were not elevated. Ovariectomy and adrenalectomy had no obvious effect on the morphology of these mammary hyperplasias. To assess possible paracrine stimulation of mammary epithelial cells (MEC) by stromal cells, we transplanted MEC from normal BALB/c mice into gland-free fat pads of Wnt-1 transgenic mice and found that normal MEC maintained their normal ductal structure in Wnt-1 fat pads without alveolar development. Further, we did not detect Wnt-1 mRNA expression in the gland-free fat pads of these transgenic mice. When Wnt-1 MEC were transplanted into the fat pads of nude mice and allowed to grow towards existing normal MEC, the morphology of the existing normal MEC remained normal. We concluded that the development of mammary hyperplasia in Wnt-1 transgenic mice is solely dependent on Wnt-1 expression in MEC. We speculate that Wnt-1 may be a growth factor for mammary gland that only acts locally on the cells that produce it.

In vitro and in vivo resistance to cisplatin in cells that have lost DNA mismatch repair.

In vitro studies have shown that loss of DNA mismatch repair due to lack of either hMSH2 or hMLH1 activity results in low-level resistance to cisplatin but not to oxaliplatin, an analogue that produces a different type of DNA adduct. No information is currently available on whether this low-level resistance is sufficient to result in enrichment of mismatch repair-deficient cells during drug exposure in vitro or to account for clinical failure of treatment in vivo. Mixed populations of cells containing a minority of DNA mismatch repair-deficient cells constitutively expressing green fluorescence protein were exposed repeatedly in vitro to cisplatin and oxaliplatin. Treatment with cisplatin resulted in a gradual enrichment for DNA mismatch repair-deficient cells, whereas treatment with oxaliplatin did not. MSH2-/- and MSH2+/+ embryonic stem cells were established as xenografts in athymic nude mice. Animals were treated 48 h after tumor implantation with a single LD10 dose of either cisplatin or oxaliplatin. MSH2-/- tumors were significantly less responsive to cisplatin than MSH2+/+ tumors, whereas there was no difference in sensitivity to oxaliplatin. These results demonstrate that the degree of cisplatin resistance conferred by loss of DNA mismatch repair is sufficient to produce both enrichment of mismatch repair-deficient cells during treatment in vitro and a large difference in clinical responsiveness in vivo. The results identify loss of DNA mismatch repair as a mechanism of resistance to cisplatin but not oxaliplatin.

An analysis of pulmonary tuberculosis data in Taiwan and Korea.

An analysis is carried out on pulmonary tuberculosis survey data from Taiwan and Korea. A mathematical model based on a Markov process is developed and used to estimate transition rates between various disease states, as well as certain 'infection parameters', which measure the strength of the relative contributions of different disease states and of endogenous reactivation to the incidence of tuberculosis in the population. It is found that endogenous reactivation plays a primary role in generating cases, followed by chronic sources of infection, particularly those with drug-sensitive organisms. Some recommendations are made with regard to optimizing treatment regimens. The methodology can easily be applied to other countries.

Effect of laser microbeam irradiation of the nucleus on the cleavage of mouse eggs in culture.

Two-cell mouse eggs were irradiated by a helium-cadmium laser on a spot of about 4 micron2 (d = 2.2 micron) in one or both nuclei either continuously or repeatedly at 0.36 erg micron-2 sec-1 and then cultured to observe cellular development. After exposing one nucleus to the microbeam to five or seven 1-sec pulses (1.80 or 2.52 ergs micron-2, respectively), about 45% developed to the 3-cell stage in 24 hr of culture. In overnight cultures of the 2-cell eggs in which both nuclei were irradiated for 9 or 20 sec continuously, 40 (9 sec) and 50% (20 sec) of the eggs remained at the 2-cell stage, while 45 (9 sec) and 25% (20 sec) developed to the 4-cell stage. Irradiating only one nucleus in a 2-cell egg by seven pulses in a spot of 4 micron2 amounting to 10 ergs reduced cleavage 45%. When both nuclei were each irradiated by a 9-sec continuous laser beam (totaling 13 ergs), about 40% of the embryos of the 2-cell stage did not divide. The effect of seven pulses on the blastomere cleavage of 2-cell mouse eggs appeared to be comparable to that of continuous 9-sec laser irradiation. Both pulse and continuous laser microirradiation methods may be developed for inactivation of the nucleus as a nonpipetting , less injurious method for enucleation of mammalian eggs.

Comparison of the BACTEC MGIT 960 with Löwenstein-Jensen medium for recovery of mycobacteria from clinical specimens.

SETTING: Taiwan Provincial Chronic Disease Control Bureau. OBJECTIVE: To evaluate the rate of recovery and the mean time to detection (TTD) of mycobacteria in clinical specimens with two culture systems, the BACTEC MGIT 960 and Löwenstein-Jensen (LJ) medium. DESIGN: We studied 365 specimens, collected from 166 patients. Specimens were processed with standard N-acetyl-L-cysteine (NALC)-NaOH method, then inoculated onto BACTEC MGIT 960 and onto LJ slants. RESULTS: A total of 124 mycobacterial isolates (114 Mycobacterium tuberculosis and 10 non-tuberculous mycobacteria) were detected. The recovery rates were 94% (117/124) with BACTEC MGIT 960 and 75.8% (94/124) with LJ. The rates of contamination for each of the systems were 5.5% with BACTEC MGIT 960 and 4.1% with LJ. The TTDs for mycobacteria were 10.7 days with BACTEC MGIT 960 and 30.6 days with LJ. Excluding the non-tuberculous mycobacteria, the TTDs for M. tuberculosis were 11.1 days with BACTEC MGIT 960 and 30.7 days with LJ. The difference in TTD between smear-positive and smear-negative specimens for either mycobacteria (10.0 vs 12.6 days; P = 0.06) or M. tuberculosis (10.1 vs 12.7 days; P = 0.06) with BACTEC MGIT 960 was not statistically significant. CONCLUSION: The BACTEC MGIT 960 system can expedite the recovery of mycobacteria in culture. Combined with conventional solid medium, it also increases the overall recovery of mycobacteria in culture.

The impact of national health insurance on the notification of tuberculosis in Taiwan.

SETTING: General notification of tuberculosis in Taiwan. OBJECTIVES: To ensure the completeness of notification of tuberculosis (TB) in Taiwan, the Bureau of National Health Insurance (NHI) introduced two policies in 1997: 1) the no-notification-no-reimbursement (NNNR) policy, and 2) the notification-fee (NF) policy. The goals of this study were to investigate the impact of the NNNR and NF policies on notification of TB. DESIGN: Review of all cases notified to the National TB Register from 1995 to 1999 to determine calendar trend, type of case and source of notification. RESULTS: There were 11,453 and 13,612 reported cases in 1995 and 1996, respectively. Following the implementation of the NHI policies, there was a 47% increase in 1997, with 20 021 reported cases. Quarterly reporting of cases reached a historic peak in the third quarter of 1997. The increase in reported cases was mainly from general hospitals/clinics. Since 1998, the number of reported cases has declined steadily, at a rate of 7% and 3% in 1998 and 1999, respectively. CONCLUSIONS: The NNNR and NF policies had a significant impact on notification of TB in Taiwan. These policies substantially improved completeness of reporting, an observation with implications for surveillance of other reported diseases.

Pulmonary resection in the treatment of patients with pulmonary multidrug-resistant tuberculosis in Taiwan.

SETTING: Chronic Disease Control Bureau, Department of Health, Taiwan. OBJECTIVE: To evaluate the role of pulmonary resection in the treatment of pulmonary tuberculosis resistant to isoniazid and rifampin (MDR-TB). DESIGN: In a retrospective cohort study, 27 MDR-TB patients who underwent pulmonary resection between December 1990 and March 1999 were reviewed. Individually-tailored treatment regimens were selected at a once-weekly staff conference following review of the patient's case history and drug susceptibility results. Surgery was performed for selected patients, essentially those: 1) whose medical treatment had failed, or for whom treatment failure seemed highly likely, or for whom post-treatment relapse seemed likely, 2) with predominantly localised disease, 3) with adequate cardiopulmonary reserve, and 4) whose treatment regimen had been composed of at least two effective drugs to diminish the mycobacterial burden. RESULTS: There was no surgical mortality apart from one peri-operative death (4%). Three patients (11%) developed complications, and 24 (92%) patients demonstrated sputum conversion and/or remained negative after surgery. Twenty-three patients have already completed treatment, and during a mean of 42 +/- 18 follow-up months (range 15-80 months), one patient relapsed. This patient was disease-free after another course of treatment. CONCLUSION: For selected patients, pulmonary resection may improve the outcome of pulmonary MDR-TB.

Growth stress distribution in leaning trunks of Cryptomeria japonica.

The distribution of growth stresses in leaning trunks of Cryptomeria japonica (L.f.) D. Don was determined by measuring the stresses released by the kerf method with strain gauges glued at specified positions along the trunks. Effects of both tree height and peripheral positions on the surface of leaning trunks on surface growth stress were determined. The inner residual growth strains in leaning trunks were also measured. We found high compression stresses in the lower side of leaning trunks that differed greatly from the tensile stresses in normal erect trunks. However, transverse compression stress was found around the tree trunk in both normal and compression wood. In leaning trees, the distribution of internal stresses in the bent trunk portion differed from that in the erect trunk portion, being compressive on the outside and tensile on the inside. The resistant moment introduced by compression stress generated in compression wood is released by the bending of the leaning trunk. The bending stresses are then superimposed on the original internal growth stress. We demonstrated that Poisson's effect of longitudinal stresses should be considered when evaluating transverse surface growth stresses. The existence and intensity of compression wood development can be assessed by growth stress measurements. We conclude that the compressing force of compression wood functions physiologically to give an upward righting response in a leaning trunk.

Right middle lobe atelectasis associated with endobronchial silicotic lesions.

BACKGROUND: In a period of 18 months, we have encountered 4 cases of right middle lobe atelectasis associated with endobronchial silicotic lesions of right middle lobe bronchi. All patients had occupational exposure to mineral dusts (3 coal miners and 1 sand blaster) for months to decades. METHODS: The nature of the endobronchial silicotic lesions that caused the bronchial obstruction has been confirmed by endobronchial biopsies and energy-dispersive spectrometry of the lesions. Extrinsic compression has been excluded by careful radiographic and computed tomographic image analysis. RESULTS: The endobronchial silicosis does not appear to correlate with the degree of pneumoconiosis of the lung parenchyma. The endobronchial silicosis may cause bronchial obstruction in the absence of radiographic evidence of pulmonary silicosis. CONCLUSION: The endobronchial silicosis and consequent lung atelectasis may be associated with silica exposure.

Rifabutin as salvage therapy for cases of chronic multidrug-resistant pulmonary tuberculosis in Taiwan.

This study was aimed at assessing the efficacy and tolerability of rifabutin for the re-treatment of cases of chronic, multidrug-resistant pulmonary tuberculosis. The study design was self-controlled, single center. Rifabutin was administered as part of an individual-tailored multidrug regimen. In-patients suffering from pulmonary tuberculosis, infected with Mycobacterium tuberculosis bacilli resistant to isoniazid, rifampicin and other drugs with progressive disease unresponsive to prior courses with standard anti-tuberculosis medications were treated. Overall, 43 patients were enrolled and treated with rifabutin at 300 or 450mg/day according to body weight in conjunction with available anti-tuberculous drugs for a mean time of 353 days (range 42-678). Of these, 36 met all eligibility criteria (i.e. positive baseline culture of sputum with bacilli resistant to rifampicin at least) and were retained for the analysis of efficacy. Seventeen patients (47%) achieved a sustained conversion to a negative culture of sputum in a mean time of 47.7 days with a range of 14-120 days. Treatment prevented deterioration in most patients and resulted in clinical and radiological cure or marked improvement in more than half of cases. No correlation was found between treatment outcome and use of medication concomitant to rifabutin or susceptibility of bacilli to the drugs used. Four deaths occurred due to disease progression, in no case being related to study drugs. Ten patients reported a total of 18 adverse events that led to treatment discontinuation in 5 cases. Rifabutin should be considered for inclusion in regimens for cases of pulmonary multidrug-resistant tuberculosis which fail to respond to previous therapy.

In vitro activity of ofloxacin against Mycobacterium tuberculosis.

For the past 3 years, ofloxacin has been widely used in treating patients with drug-resistant tuberculosis in Taiwan. To study its usefulness in treating these patients, 139 isolates of Mycobacterium tuberculosis from patients treated at the Taiwan Provincial Chronic Disease Control Bureau from September 1994 to September 1995 were tested to determine the in vitro antituberculosis activity of ofloxacin. Of these, 131 had not been previously exposed to ofloxacin, and 130 (99.2%) were susceptible to ofloxacin. Sixty-four isolates were found to be susceptible to all conventional antituberculosis drugs, and all of these were also susceptible to ofloxacin. Of the remaining 67 isolates that were resistant to one or more conventional antituberculosis drugs, 66 (98.5%) were susceptible to ofloxacin. There was no association between susceptibility to ofloxacin and susceptibility to conventional antituberculosis drugs among the isolates tested. Of the eight isolates of M. tuberculosis previously exposed to ofloxacin, seven (87.5%) were resistant. Our results indicate that patients with multidrug-resistant strains of M. tuberculosis who have not received prior ofloxacin treatment may be safely treated with ofloxacin even without knowing the result of pretreatment ofloxacin susceptibility tests. We also found that ofloxacin resistance emerges frequently. Therefore, an adequate combination of antituberculosis drugs, along with ofloxacin, should be prescribed to prevent the development of resistance to ofloxacin.

Current role of surgery in the management of pleuropulmonary tuberculosis.

This article reviews the recent surgical treatment of patients with pleuropulmonary tuberculosis in the northern Taiwan area. With the advent of effective chemotherapeutic agents and fewer failed medical treatments, the need for surgery has decreased. During the period 1985 to 1991, a total of 62 patients in the northern Taiwan area received surgical treatment for lesions or complications associated with pleuropulmonary tuberculosis. In the majority of cases, patients underwent operations for undiagnosed tumors. Other indications for surgery included tuberculosis cavity with aspergilloma, localized cavity or anatomic residue with a positive acid fast bacilli smear, complications with altered anatomy secondary to tuberculosis and chronic tuberculous empyema. The appropriate selection of patients for surgical intervention should ensure satisfactory surgical results. Surgery continues to play a vital role in the management of certain patients with pleuropulmonary tuberculosis.

In vitro activity of rifabutin and rifampin against clinical isolates of Mycobacterium tuberculosis in Taiwan.

BACKGROUND AND PURPOSE: To determine the in vitro activity of rifabutin against Mycobacterium tuberculosis (MTB) and the cross-resistance rate between rifampin and rifabutin. METHODS: A total of 56 clinical isolates of MTB, including 23 multidrug-resistant (MDR) isolates and 33 susceptible isolates, were tested for susceptibility to rifampin and rifabutin using the absolute concentration method. The concentrations of drugs tested were 2.5 and 5 mg/mL for rifampin and 0.1, 0.5, 1, 2.5, 5, and 10 mg/mL for rifabutin. RESULTS: All 33 MTB isolates that were susceptible to rifampin were also susceptible to rifabutin. None of the 23 MDR-MTB isolates were inhibited by rifabutin at a concentration of 0.1 mg/mL. Among these 23 MDR isolates, three were susceptible to rifabutin at concentrations > or = 0.5 mg/mL, six were susceptible to rifabutin at concentrations > or = 5 mg/mL, 18 were susceptible to rifabutin at concentrations > or = 10 mg/mL and five were not inhibited at any of the concentrations tested. The cross-resistance rate between rifampin and rifabutin was 87%. CONCLUSIONS: Our results indicate that the in vitro activity of rifabutin against drug-susceptible MTB isolates is greater than that of rifampin. For MDR-MTB isolates, the cross-resistance is high between rifampin and rifabutin.