An investigation of patients with pulmonary tuberculosis in Kuwait in preparation for studies of immunotherapy with Mycobacterium vaccae.

Sixty-five patients, many of them immigrant to Kuwait, with bacteriologically proven, adult type, pulmonary tuberculosis were studied by many parameters over the 4 months following diagnosis. Twelve were infected with tubercle bacilli resistant to at least one anti-tuberculosis drug. Preliminary evidence suggested that this was frequently primary resistance in patients infected in their countries of origin. The Kuwaiti environment results in very high skin test and lymphocyte proliferative responses (LTT) to shared and species specific antigens of mycobacteria in healthy persons. In comparison, patients with tuberculosis lacked cellular responses to group i and group ii antigens, but had increased IgG and IgA binding to mycobacterial antigens in general. LTT responses to added interleukin 2, and production of alpha interferon, were normal in our patients, but induction of gamma interferon in response to phytohaemagglutinin was reduced initially, rising towards normal during treatment. Biochemical and haematological abnormalities present at the time of diagnosis rapidly corrected. The disease differed from that reported in most previous studies in that fever was uncommon, the disease was never fatal, and most tuberculin tests were not necrotising. This implied that a detrimental immunopathological component is less pronounced in those exposed to the Kuwaiti environment, and a hypothesis is put forward to explain this.     

Immunotherapy with Mycobacterium vaccae as an adjunct to chemotherapy in the treatment of pulmonary tuberculosis

47 patients with adult-type pulmonary tuberculosis attending the Chest Diseases Hospital in Kuwait were given a single injection of 10(9) irradiation-killed M. vaccae after 1 month of a 9-month course of chemotherapy. The patients were followed-up for 3 more months in double blind comparison with 65 patients given an injection of saline (placebo). The immunotherapeutic injection produced a small local lesion in 44/47 patients, 18 of which ulcerated and produced small scars. Immunotherapy made no measurable difference to the bacteriological, biochemical, haematological, or radiological parameters measured. However it was associated with significantly improved weight gain, reduced size of skin test response to Tuberculin, increased lymphocyte proliferation to common mycobacterial antigens, and increased antibody levels to mycobacterial antigens. The changes in skin test and LTT responses were related and occurred in 29% of patients whose recognition of common mycobacterial antigens returned to normal. The remaining patients did not differ in these respects from those receiving placebo. The proportion of patients whose responses were improved was very similar to that achieved using the same immunotherapeutic agent in a group of treated multibacillary leprosy patients.     

Abdominal and pelvic extra-adrenal paraganglioma: a review of literature and a report on 7 cases

INTRODUCTION: Extra-adrenal paraganglioma (pheochromocytoma) is a rare tumor. Herein we describe the clinical and pathological findings in patients with paragangliomas of the urinary bladder, seminal vesicle and retroperitoneum. METHODS: Between January 1994 and January 2001, extra-adrenal paragangliomas were diagnosed in 7 patients: 3 males and 4 females. The mean age of our patients was 32 +/- 15.9 years. We reviewed the clinical data. Urinary metanephrines and vanillyl mandelic acid and blood catecholamine levels were estimated in 4 cases. CT scan and/or MRI were used in the imaging of all cases. 123I-MIBG was used in only 1 patient, who harbored multiple tumors. All the patients but one underwent surgical treatment. RESULTS: The definitive diagnosis was made by histopathological examination of the removed tumors and was confirmed in all cases by the immunohistochemical stains of chromogranin A and S100 protein. There was metastasis in the pelvic lymph nodes in 1 patient. Follow-up ranged from 3 to 82 months (mean = 37.9 +/- 25.8). The catecholamine level was elevated in 3 patients under basal conditions and during endoscopic resection of the tumor in a fourth patient. In all cases, the catecholamine level was normalized after surgery. There was no recurrence or metastasis in any case following surgery. CONCLUSION: Pre-operative diagnosis of nonfunctioning bladder paraganglioma is difficult, but the tumors should be suspected in patients who have hypertension, hematuria or mass effects due to the tumor growth in the pelvis and/or retroperitoneum. Six of the seven cases reported here were found in the usual locations: 3 in the urinary bladder, 2 in the renal hilum and 1 in the organ of Zuckerkandl. One patient had multiple tumors, including a paraganglioma of the seminal vesicles. Resection is the treatment of choice, and in the case of urinary bladder paraganglioma should include total cystectomy. In patients with unresectable multiple tumors, medical therapy may be used to control hypertension.     

Engraftment of bone marrow and fetal liver cells after in utero transplantation in MDX mice

Background/Purpose: In utero hematopoietic stem cell transplantation (IUHSCTx) has been experimentally or clinically effective only in circumstances in which there is a survival advantage for donor cells. A survival advantage exists for normal muscle cells in muscular dystrophy. Because hematopoietic and mesenchymal stem cells may have the capacity to differentiate into muscle cells, the authors hypothesized that in utero bone marrow (BM) or fetal liver (FL) stem cell transplantation may be used to treat muscular dystrophy. Methods: Time-dated 14-day-gestation fetal muscular dystrophy mice (mdx) were injected intraperitoneally with 1 to 5 [times ] 10⁶ BM or FL cells per fetus from Rosa26 donor mice (transgenic for lacZ). Four weeks after birth, peripheral blood from the pups was analyzed for hematopoietic chimerism by using fluorescence-activated cell sorting (FACS) for the Ly-9.1 marker. Chimeric mice (6 BM and 2 FL recipients) were sacrificed at 12 to 14 months of age, muscles were stained with X-gal, and analyzed by 1- to 2-[mu ]m plastic sections. Polymerase chain reaction (PCR) for lacZ was performed in other organs to determine systemic engraftment. Results: At the time of death, all animals that were chimeric at 4 weeks continued to show hematopoietic chimerism of 0.2% to 9% by FACS. Engrafted donor cells were found in multiple sections from hindlimb skeletal muscles, diaphragms, and hearts from both BM and FL recipients. These cells had incorporated into the host muscles, and their morphology was consistent with myogenic differentiation. PCR of BM, liver, spleen, thymus, kidney, and lung for lacZ was positive in multiple animals. Conclusions: IUHSCTx leads to widespread engraftment of donor cells in multiple muscle compartments of hematopoietic chimeras. The advantage for normal myocytes offered in the mdx model allows engraftment and myogenic differentiation of transplanted BM or FL cells by morphology at a relatively higher frequency in muscle relative to other tissues, without the need for host conditioning. Because muscular dystrophy now can be detected early in gestation, such a strategy may offer a future alternative in the clinical treatment of this disease. J Pediatr Surg 37:1058-1064.     

Pharacine,a natural p-cyclophane and other indole derivatives from Cytophaga sp. strain AM13.1

From the ethyl acetate extract of the bacterial strain Cytophaga sp. AM13.1, among many known compounds, the new natural products 2,5-bis(3-indolylmethyl)pyrazine (2) and a highly symmetrical p-cyclophane named pharacine (5) were identified. In addition, tryptamine isovalerate (1) and p-hydroxyphenylacetamide (4), known as plant metabolites, were isolated and characterized from a microorganism for the first time. The new natural products showed no activity against three microalgae, the fungus Mucor miehei, the yeast Candida albicans, and the bacteria Staphylococcus aureus, Bacillussubtilis, Escherichia coli, and Streptomyces viridochromogenes.     

Post traumatic laryngeal incompetence

Self-inflicted laryngeal injuries are rare. This is a case of attempted suicide with a knife. The patient was brought into A&E and initial attempts at repair of the laryngo-skeletal structures were performed Later it became evident that the patient had an insensate hypofunctioning larynx. We present a technique aimed at rehabilitating the poorly functioning, incompetent larynx without the necessity for a permanent tracheostomy or laryngectomy. A single surgical procedure combining a cricopharyngeal myotomy, an anterior hyoid suspension and vocal fold angmentations was performed in an attempt to avoid a laryngectomy in non-malignant pathology. The long-term results of this surgery would need to be subjected to further evaluation.     

Torsion of a hernia sac invaginating into the tunica vaginalis and resembling testicular torsion

A 12-year-old boy was operated upon for torsion of a hernia sac invaginating into the tunica vaginalis. His clinical presentation resembled that of testicular torsion. Correspondence to: K. Kimura     

Cardiopulmonary bypass temperature and brain function

A debate has emerged in recently published studies about the optimum cardiopulmonary bypass temperature for good neurological outcome - warm vs. cold, i.e. normothermic vs. hypothermic. Although many comparative studies have been performed, the results of these studies are inconclusive and are difficult to interpret. Brain function has been studied in terms of neurological and neuropsychological outcome, protein S100beta levels as a marker of brain damage, and cerebral oxygenation using jugular bulb oximetry and near-infrared spectroscopy. The studies produce no conclusive proof of the superiority of warm or cold cardiopulmonary bypass. However, it appears that any degree of bypass hypothermia (< 35 degrees C) may protect the brain. On the other hand, even a slight increase in bypass temperature to > 37 degrees C may cause marked brain injury.     

Differentiation of renal cell carcinoma subtypes by multislice computerized tomography

Purpose

We differentiated renal cell carcinoma subtypes using multislice computerized tomography (CT).

Materials and Methods

We reviewed the CT images of 87 patients with renal cell carcinoma. Three subtypes of renal cell carcinoma were noted, including clear cell in 37 cases, papillary in 26 and chromophobe in 24. Biphasic CT (unenhanced, corticomedullary and excretory phases) was done in all patients. We compared patient age and sex, tumor size, enhancement degree and pattern (homogeneous, heterogeneous and predominantly peripheral), the presence or absence of calcification or cystic degeneration (necrotic or hemorrhagic areas within the tumor) and tumor spreading patterns, including perinephric change, venous invasion and lymphadenopathy, in the 3 subtypes.

Results

The degree of enhancement was significantly different among the 3 subtypes in the corticomedullary and excretory phases (p <0.001). Cystic degeneration was more evident in the clear cell subtype than in the other subtypes regardless of tumor size (p <0.001). A hypervascular pattern (higher tumor enhancement after contrast material injection due to higher vascularity) was noted in 48.6% of clear cell subtype in comparison to 15.4% of papillary and 4.2% of chromophobe subtypes (p <0.001). The chromophobe subtype showed homogeneous enhancement in 75% of cases in comparison to 45% and 65% of clear cell and papillary subtypes (p >0.05). Calcification was evident in 21.6%, 23.1% and 25% of clear cell, papillary and chromophobe subtypes, respectively (p >0.05).

Conclusions

To differentiate the subtypes of renal cell carcinoma the degree of enhancement is the most valuable parameter. The presence or absence of cystic degeneration, vascularity and enhancement patterns can serve supplemental role in differentiating renal cell carcinoma subtypes.     

Overexpression of cyclins A and B as markers of neoplastic glandular lesions of the cervix

INTRODUCTION: Cyclins are a family of regulatory proteins that play a pivotal role in controlling the cell cycle. While there is evidence of their altered expression in cervical squamous lesions, their precise role in glandular neoplasia is yet to be elucidated. OBJECTIVES: To investigate the role of cyclins as markers of early cervical glandular neoplasia by comparing their expression in lesions of different histological type. METHODS: Through a cross-sectional analytical study, paraffin wax sections of normal cervix (n = 11), endometriosis/tubo-endometrioid metaplasia (TEM) (n = 19), cervical glandular intraepithelial neoplasia (CGIN) (n = 33), and invasive adenocarcinoma (n = 28) were studied using monoclonal antibodies for cyclins A, B, D, and E with heat pretreatment for antigen unmasking. A quantitative assessment was employed for the analysis of percentage expression of each marker. Statistical analysis of data was performed using SPSS. RESULTS: A progressive significant increase in cyclin A expression occurred from normal cervix (median: 0, IQ: 0-0), through endometriosis/TEM (median: 1, IQ: 0-15) and CGIN (median: 15, IQ: 0-30) to invasive adenocarcinoma (median: 40, IQ: 21.25-60). Cyclin B exhibited a similar pattern (median: 0, IQ: 0-0, median: 0, IQ: 0-0.5, median: 8, IQ: 0.75-15, and median: 30, IQ: 15-45, respectively). Statistically higher expression of cyclin B was found in CGIN than in TEM/endometriosis (P < 0.001). Invasive adenocarcinomas expressed higher levels of cyclins A and B than CGIN (P < 0.001). There was significantly greater cyclin E expression in TEM/endometriosis than in normal cervix (P = 0.03) with a nonsignificant further increase in CGIN and invasive adenocarcinoma. The expression of cyclin D was not significantly different among all groups. CONCLUSIONS: Our data indicate that up-regulation of cyclin A and B expression occurs in neoplastic lesions of the cervix. Cyclin B expression was significantly more widespread in CGIN lesions than in TEM/endometriosis indicating that further assessment of the value of this marker in the diagnosis of cervical glandular neoplasia is warranted.