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Biomedical subjects

J Junge

Publications and source records attributed to J Junge.

At least 19 recordsLinked to original sources

Alveolar damage in AIDS-related Pneumocystis carinii pneumonia.

OBJECTIVE: Pneumocystis carinii pneumonia is the most common and serious of the pulmonary complications of AIDS. Despite this, many basic aspects in the pathogenesis of HIV-associated P carinii pneumonia are unknown. We therefore undertook a light and electron microscopic study of transbronchial biopsy specimens to compare pathologic features of P carinii pneumonia and other HIV-related lung diseases. DESIGN AND PATIENTS: Thirty-seven consecutive HIV-infected patients undergoing a diagnostic bronchoscopy. RESULTS: P carinii pneumonia was characterized by an increase in inflammation, edema, exudate, fibrosts, type II pneumocyte proliferation, and cellular infiltration of the alveolar wall when compared with other lung diseases (all p < 0.05). Electron microscopy showed apposition of the trophozoite to the type I pneumocyte. Erosion of type I pneumocytes was observed in 13 of 15 patients with P carinii pneumonia, whereas none without P carinii pneumonia had this finding (p < 0.05). Erosion of the type II pneumocyte was not observed. CONCLUSION: Inflammation, interstitial fibrosis, and alveolar epithelial erosion are characteristic features of P carinii pneumonia. The changes may form the pathologic basis for the respiratory failure seen in patients with P carinii pneumonia. Electron microscopy did not show any diagnostie advantage over conventional light microscopy using routine stains.

AIDS-Related Opportunistic Infections

Pituitary adenylate cyclase activating polypeptide (PACAP): occurrence and vasodilatory effect in the human uteroplacental unit.

UNLABELLED: Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide which was originally isolated from ovine hypothalamus. PACAP exists in at least two biologically active forms, PACAP-38 and PACAP-27. The aim of this study was to establish the distribution, localization and smooth muscle effects of PACAP-38 and PACAP-27 in the human uteroplacental unit. For this purpose we used radioimmunoassay, immunocytochemistry and in vitro studies of the effect of the peptides on smooth muscle activity. RESULTS: By radioimmunoassay both peptides were detected throughout the uteroplacental unit. The concentrations of PACAP-27 were in general low, ranging from 1/6-1/25 of the corresponding PACAP-38 concentrations. PACAP-immunoreactivity was localized in nerve fibres of the lower segment of the pregnant uterus, but the number of PACAP-immunoreactive nerves was very clearly reduced compared to the corresponding isthmic region of non-pregnant myometrial tissue. PACAP-immunoreactive fibres were not observed in placenta or in the umbilical cord. Both PACAP-38 and PACAP-27 caused a concentration-dependent relaxation on stem villous arteries and on the intramyometrial arteries. Neither of the peptides displayed any effect on non-vascular smooth muscle specimens from the term pregnant myometrium. In conclusion the findings suggest a vasoregulator role of PACAP in the human uteroplacental unit.

Adult

[Prognostic value of interleukin-8 in AIDS-related Pneumocystis carinii pneumonia].

UNLABELLED: We evaluated the significance of interleukin-8 (IL-8) in Pneumocystis carinii pneumonia (PCP). Bronchoalveolar lavage (BAL) fluid and serum was prospectively collected in 76 consecutive HIV-infected patients with a primary episode of PCP, as well as in ten healthy control subjects. Patients were found to have elevated levels of IL-8 in BAL fluid compared to control subjects (p < 0.01). Nine patients died during the course of PCP. Non-survivors had significantly higher IL-8 levels in BAL fluid than survivors (p < 0.05). Furthermore patients with levels of IL-8 in BAL greater then 90 pg/ml (i.e. greater than control subjects) had significantly worse vital prognosis (log rank test, p < 0.05). Thirteen patients required mechanical ventilation (MV), and these patients had significantly elevated levels of IL-8 compared with patients not requiring MV (p < 0.05). IN CONCLUSION: i) IL-8 in BAL fluid correlates to the clinical severity of the pneumonia, and ii) is a predictor of mortality and severe respiratory compromise.

AIDS-Related Opportunistic Infections

Human papillomaviruses and multifocal genital neoplasia.

In 143 patients with vulvar carcinoma (76 cases) or vulvar intraepithelial neoplasia (VIN III, 67 cases), cervical cancer or cervical intraepithelial neoplasia CIN III lesions developed in 39 patients (27%) at some time during their life. In patients with classic keratinizing squamous cell carcinoma (KSC) of the vulva, cervical neoplasia developed in only one of 51 (2%), whereas the frequency was 10 of 25 (40%) in patients with vulvar carcinoma of the basaloid or warty type and 28 of 67 (42%) in patients with VIN III lesions. The original, paraffin-embedded surgical specimens were examined by polymerase chain reaction and type-specific molecular hybridization for human papillomavirus (HPV) DNA of the types 6, 11, 16, 18, and 33. DNA of the oncogenic types HPV 16 or HPV 33 was found in 4% of the KSCs, in 84% of the basaloid or warty carcinomas, in 90% of VIN III lesions, and in 89% of the cervical lesions. The same HPV type was found in both lesions in 81% of the patients with double primary tumors. The results support the concept that VIN III and a subgroup of vulvar carcinomas are HPV-related lesions, that they are frequently associated with another HPV-related genital primary tumor, and that these multiprimary tumors are secondary to an HPV infection involving the entire genital tract.

Adult

Vulvar intraepithelial neoplasia III: a viral disease of undetermined progressive potential.

Seventy-three patients with vulvar intraepithelial neoplasia (VIN) grade III were followed for a median of 5 years after primary treatment. Thirty women also had a diagnosis of cervical neoplasia. During the follow-up 26 patients (36%) had one or more vulvar recurrences. Recurrences were seen significantly more often in the patients who also had cervical neoplasia, indicating a common etiology. Microinvasive carcinoma developed in 12 patients, 3 of whom later developed frankly invasive vulvar cancer. The original, paraffin-embedded vulvar specimens were examined by the polymerase chain reaction for human papillomavirus DNA of the types HPV 6, 11, 16, 18, and 33. HPV types 16 and 33 were found in 90% of the VIN lesions. It is concluded that VIN III is an HPV-related disease in all or almost all cases, and that a generalized genital HPV infection may be a factor in the development of multicentric genital neoplasia. No association was observed between the specific HPV type and the risk of recurrent vulvar disease, cervical neoplasia, or malignant progression.

Adult

Management of low-grade CIN: follow-up or treatment?

OBJECTIVE: To examine whether low-grade cervical dysplasia carries a higher risk of progression when associated with the cancer-related human papillomavirus types 16, 18, 31 or 33. STUDY DESIGN: Retrospective, with PCR-based HPV diagnosis on the original cervical biopsies from 71 patients with CIN I and II. CIN III developed in 34 lesions, and 37 showed complete regression during non-invasive follow-up. RESULTS: Progression occurred in 15/41 CIN I and in 19/30 CIN II lesions (P = 0.03). HPV DNA was detected in 43 specimens. CIN III developed in 25% of HPV-negative lesions, in 48% of HPV-positive CIN I lesions, and in 77% of HPV-positive CIN II lesions. CONCLUSION: Low-grade lesions are at higher risk of progression when associated with HPV types 16, 18, 31 or 33 (P = 0.002). HPV diagnosis can be useful in the triage of patients with low-grade CIN.

Adolescent

Interleukin-8 and eicosanoid production in the lung during moderate to severe Pneumocystis carinii pneumonia in AIDS: a role of interleukin-8 in the pathogenesis of P. carinii pneumonia.

Pneumocystis carinii pneumonia (PCP) may cause severe respiratory distress. This is believed to be partly caused by the accumulation of neutrophils in the lung. Interleukin-8 (IL-8) and leukotriene B4 (LTB4) are potent neutrophil chemo-attractants and activators. Eicosanoids [i.e. prostaglandins (PG) and leukotrienes (LT)] are pro-inflammatory mediators released from arachidonic acid by action of phospholipase A2 (PLA2) and have been implicated in the host response to micro-organisms. Bronchoalveolar lavage (BAL) was performed on patients with PCP as part of a randomized study of adjuvant corticosteroids vs. placebo, in addition to standard antimicrobial therapy. Re-bronchoscopy was offered at day 10. BAL fluid was available for 26 patients who had follow-up bronchoscopy performed. At diagnosis, IL-8 levels were elevated in patients with PCP, compared to healthy controls, and correlated with relative BAL neutrophilia and P(A-a)O2. LTB4 was also elevated in PCP, but failed to correlate with either BAL neutrophilia or P(A-a)O2. PLA2 activity in patients correlated with IL-8 levels and BAL neutrophilia, but not with P(A-a)O2. A trend towards a decrease in IL-8 levels in BAL fluid was detected in the corticosteroid-treated patients from days 0-10, whereas no change was detected in the placebo group. No change in levels of LTB4, LTC4, PGE2, PGF2a and PLA2 were detected cover time in either treatment group. This study establishes a correlation between IL-8, BAL neutrophilia and P(A-a)O2, and suggests a role of IL-8 as a mediator in the pathogenesis of PCP, whereas the role of eicosanoids seems less clear.

AIDS-Related Opportunistic Infections

Analgesic and hemodynamic effects of epidural clonidine, clonidine/morphine, and morphine after pancreatic surgery--a double-blind study.

This study characterizes analgesia an hemodynamics after epidural clonidine 8 micrograms/kg (Group C) or clonidine 4 micrograms/kg+morphine 2 mg (Group CM) in comparison to epidural morphine 50 micrograms/kg (Group M). Forty-five patients scheduled for pancreatectomy in combined general/epidural anesthesia were studied. The study drugs were administered 75 min postoperatively and for 10 h pain intensity (visual analog scale [VAS]), heart rate (HR), mean arterial pressure (MAP), and cardiac output (CO) were measured; filling pressures were kept > 5 mm Hg. Adequate analgesia could be achieved within 1 h in all patients of Groups C and CM, but only in six patients of Group M (P < 0.001). Quality of analgesia was comparable in all groups (VAS reduction 82% +/- 20%, mean +/- SD) but duration of analgesic action was longer in Groups CM (586 +/- 217 min) and M (775 +/- 378 min) compared to Group C (336 +/- 119 min) (P < 0.001). In Group M, no hemodynamic alterations occurred. In Groups C and CM, HR, CO, and MAP were reduced significantly compared to baseline within the first 15-90 min, while stroke volume and systemic vascular resistance remained stable. We conclude, that hemodynamic alteration after epidural clonidine under conditions of stable filling pressures is caused mainly by a decrease in HR. It is not an effect of analgesia but of the intrinsic antihypertensive action of clonidine.

Analgesia, Epidural

Pituitary adenylate cyclase-activating polypeptide: occurrence and relaxant effect in female genital tract.

The distribution, localization, and smooth muscle effects of pituitary adenylate cyclase-activating polypeptide (PACAP) were studied in the human female genital tract. The concentrations of PACAP-38 and PACAP-27 were measured by radioimmunoassays, and both peptides were found throughout the genital tract. The highest concentrations of PACAP-38 were detected in the ovary, the upper part of vagina, and the perineum. The concentrations of PACAP-27 were generally low, in some regions below the detection limit and in other regions 1 to 5% of the PACAP-38 concentrations. Immunocytochemistry revealed that PACAP was located in delicate varicose nerve fibers that were most abundant in the internal cervical os, where they mainly seemed to innervate blood vessels and smooth muscle cells. PACAP-38 and PACAP-27 (10(-10)-10(-6) M) caused a concentration-dependent relaxation of the spontaneous activity of the nonvascular smooth muscle strips from fallopian tube and myometrium in vitro. Likewise, both peptides (10(-10)-10(-6) M) caused relaxation of nonrepinephrine (10(-6) M)-precontracted intramyometrial arteries. No effect of the PACAP sequences, PACAP-(6-27), PACAP-(16-38), and PACAP-(18-27), on fallopian tube was observed. The findings suggest a smooth muscle regulatory role of PACAP in the human female reproductive tract.

Adolescent

Prognostic value of interleukin-8 in AIDS-associated Pneumocystis carinii pneumonia.

UNLABELLED: Interleukin-8 (IL-8) is a potent neutrophil chemoattractant and activator. Pneumocystis carinii pneumonia is associated with an accumulation of neutrophils in bronchoalveolar lavage (BAL) fluid. Thus, we hypothesized that IL-8 is involved in the pathogenesis of P. carinii pneumonia. BAL fluid and serum were prospectively collected in 76 consecutive HIV-infected patients with a primary episode of P. carinii pneumonia, as well as in 10 healthy control subjects. Patients were found to have elevated levels of IL-8 in BAL fluid compared with control subjects (p < 0.01). Nine patients died during the course of P. carinii pneumonia. Comparing survivors with nonsurvivors, the median IL-8 level in BAL fluid was 127 (0 to 3,900) versus 584 (127 to 6,100) pg/ml (p < 0.05). Furthermore, patients with levels of IL-8 in BAL fluid greater than 90 pg/ml (i.e., greater than control subjects) had significantly worse vital prognosis (log rank test, p < 0.05). Thirteen percent required mechanical ventilation (MV). Patients requiring MV had a median IL-8 level of 396 (25 to 6,100) versus 129 (0 to 3,900) pg/ml for patients not requiring MV (p < 0.05). IN CONCLUSION: i) IL-8 in BAL fluid correlates to the clinical severity of the pneumonia, and ii) is a predictor of mortality and severe respiratory compromise.

AIDS-Related Opportunistic Infections

Vulvar squamous cell carcinoma and papillomaviruses: indications for two different etiologies.

The vulvectomy specimens of 78 patients with vulvar squamous cell carcinoma were reviewed and examined for human papillomavirus (HPV) types 6, 11, 16, 18, and 33 by the polymerase chain reaction technique. The tumors were classified as keratinizing squamous cell carcinoma (KSC), as warty carcinoma (WC), and as basaloid carcinoma (BC). DNA of HPV types 16 and 33 was found in 2/51 KSC, in 12/17 WC, and in 10/10 BC. HPV types 6, 11, and 18 were not detected. Patients with WC and BC were younger, and 78% had VIN III lesions adjacent to the carcinoma. Patients with KSC were older and had a high incidence of dystrophic lesions, including lichen sclerosus, adjacent to the tumor. None of the KSC showed adjacent VIN III. In conclusion, vulvar carcinoma segregates into two categories, of which KSC seems to be the classic type, only rarely associated with HPV infection, and mostly affecting older women; WC and BC constitute an HPV-related subgroup of tumors occurring in younger patients and are associated with VIN III lesions from which they may emerge.

Adult

Pleurodesis with polidocanol in pigs. An experimental study.

Polidocanol was instilled in five pleural cavities of three pigs. Adhesions formed in all. Adhesion distribution varied from covering a minor part to most of the lung, depending on the amount of polidocanol. One control cavity treated with sodium chloride was unaffected. Microscopy showed fibrous bridges between the pleural layers and mild submesothelial fibrosis and inflammation.

Animals

Cervical koilocytosis and high risk HPV types: the benefit of laser vaporization.

Forty-six patients with biopsy-proven cervical koilocytosis, which in 19 cases was associated with CIN I, were randomized to treatment by cervical laser vaporization or to follow-up without therapy. The polymerase chain reaction was used to examine the paraffin-embedded cervical biopsies for human papillomavirus (HPV) types 6, 11, 16, 18 and 33 by polymerase chain reaction and molecular hybridization technique. Twenty biopsies contained HPV DNA, in 17 cases of the putatively oncogenic types HPV 16 and HPV 18. During a mean follow-up of 28 months, the lesions resolved in 37 women, 5 women had progression to CIN III lesions, and 4 women had persisting disease. Lesions not harboring any of the 5 HPV types showed a high spontaneous regression rate of 88%, which was not improved by the laser therapy. In the HPV-positive lesions, resolution occurred in only 29% of untreated lesions, but in 92% of those treated by laser. The difference is significant (P = 0.007). It is concluded that in patients with cervical koilocytosis, the HPV diagnosis could be of practical value in identifying patients who might benefit from treatment.

Adult

Amount of Pneumocystis carinii and degree of acute lung inflammation in HIV-associated P carinii pneumonia.

Correlations between semiquantitative amounts of Pneumocystis carinii (PC), the degree of inflammation, and the severity of pneumonia were analyzed in 58 patients with PC pneumonia (PCP). Material from both transbronchial biopsies (TBBs; n = 39) and bronchoalveolar lavage fluid (BALF; n = 57) was examined. In the TBB the amount of PC correlated strongly with overall inflammation in the interstitium (Kendall correlation coefficient [Kcc] = 0.59; p < 0.0001), type 2 pneumocyte proliferation, and edema formation. The amount of PC in the TBB also correlated with interstitial accumulation of neutrophils (Kcc = 0.54; p = 0.0001), lymphocytes, and macrophages. In BALF the amount of PC correlated with edema formation and type 2 pneumocyte proliferation in the TBB but not with the percentage of neutrophils, lymphocytes, or macrophages in BALF. The amount of PC in the BALF and the percentage of neutrophils in the BALF correlated significantly with Po2 and the serum lactate dehydrogenase (LDH) level. Neither short-term nor long-term survival was affected by the amount of PC, inflammatory markers in the TBB, inflammatory cells in BALF, Po2, or the serum LDH levels. In conclusion, the amount of PC is associated with the extent of the acute inflammatory reaction in the lung in PCP associated with human immunodeficiency virus (HIV).

Adult

Tumours classified as "malignant histiocytosis" in children are T-cell neoplasms.

During the last five years increasing evidence has accumulated that many tumours classified as 'histiocytic' in the past do not originate from macrophages, but from transformed (or anaplastic) large lymphoid cells. Most of these studies have focused upon adult neoplasms. Knowledge concerning the lineage of 'histiocytic' tumours in the paediatric age group is more limited. In this study we have examined the clinical, morphological and immunophenotypical features of six childhood malignancies originally diagnosed as being of histiocytic origin. Three patients showed an aggressive course with involvement of internal organs and very short survival times. Two patients were brought into remission: one is alive without active disease after seven years; the other died after seven years due to treatment-related cardiomyopathy. The remaining patient had a protracted course for two and a half years, but subsequently deteriorated and died three years after diagnosis. The histomorphological features in five cases were those of anaplastic large cell lymphomas. The remaining case consisted of pleomorphic (rather than anaplastic) large lymphoid cells. In all cases the immunophenotypical examination showed features characteristic of activated T lymphocytes. All cases were positive for Ki-1 (CD30), and three were positive for epithelial membrane antigen (EMA). Histiocyte-associated markers were positive in residual reactive macrophages, but nowhere could unequivocal positivity for macrophage-associated markers be seen in the neoplastic cells. It is concluded that most childhood malignancies in the past classified as 'histiocytic' are examples of anaplastic large cell (Ki-1) lymphomas of T-cell type and that true histiocytic malignancies are exceedingly rare in the paediatric age group.

Antigens, CD

[3 cases of visceral leishmaniasis, one in a HIV-positive man].

Three cases of visceral leishmaniasis (kala-azar) are presented. One of these was in a 43-year-old patient with AIDS who was infected in Southern Spain. Another was in a man aged 25 years infected in West Africa. These cases are the first two adults to be reported in Denmark. The third case was an 18 month old previously healthy boy, infected in Southern Spain. The symptomtology, diagnosis and treatment of the disease are discussed and it is stressed that serological diagnostic tests have limited value in HIV positive patients.

Acquired Immunodeficiency Syndrome