Aliya N. Husain

Low rate of acute lung allograft rejection after the use of daclizumab, an interleukin 2 receptor antibody.

Background. The incidence and the severity of acute lung allograft rejection has been linked to the development of bronchiolitis obliterans syndrome. Therefore, we investigated the effects of daclizumab, a humanized monoclonal antibody directed against the alpha subunit of the interleukin 2 receptor, in reducing acute rejection after transplantation. Methods. We retrospectively evaluated 27 patients who received daclizumab as induction immunosuppression and compared them with a historical control group of 34 patients. Both groups received similar immunosuppressive regimens involving tacrolimus, prednisone, and either azathioprine or mycophenolate mofetil. All patients received cytomegalovirus and aspergillus prophylaxis. Results. Twenty-one patients in the control group and 22 patients in the daclizumab group were available for analysis at 6 months after lung transplantation. Ten (48%) patients in the control group had at least grade 2 acute rejection compared with four (18%) in the daclizumab group (P <0.04). The incidence of infection was similar in both groups. One patient in each group developed posttransplant lymphoproliferative disease. Conclusion. Therapy with daclizumab resulted in a significant decrease in the incidence of grade 2 or greater acute rejection after lung transplantation compared with historical controls. There seems to be no increase in the incidence of adverse effects in the patients treated with daclizumab.

Mesenteric defects as a cause of intestinal volvulus without malrotation and as the possible primary etiology of intestinal atresia

Mesenteric defects can lead to intestinal volvulus even when the midgut is normally rotated. There are two types of mesenteric defects: basilar, in which the entire base of the mesentery is involved, and segmental, in which only an isolated portion of the mesentery is affected. These defects can present at any age, and the clinical symptoms depend on the extent of the disease and the amount of intestine involved in the volvulus. In the newborn, the basilar defects have clinical signs and symptoms similar to those of midgut volvulus secondary to malrotation. Similar to midgut volvulus secondary to malrotation, this is a surgical emergency. In older patients, basilar defects can be misdiagnosed because of the normal placement of the ligament of Treitz and because of failure to consider mesenteric defects as a possible cause. The treatment for basilar mesenteric defects is intestinal fixation. Intestinal volvulus secondary to segmental defects always presents as intestinal obstruction. In the newborn, these lesions may be indistinguishable from intestinal atresia. Older children present with intestinal obstruction of an unknown cause. Resection of the affected intestine is the treatment for segmental mesenteric defects. Intestinal mesenteric abnormalities as a cause of intestinal atresia unifies under one etiology all the lesions observed in intestinal atresia. Although this theory does not rule out other causes of intestinal atresia, intestinal mesenteric defects may be the primary condition under which intestinal atresia occurs.

Neonatal Pulmonary Hypoplasia: An Autopsy Study of 25 Cases

Pulmonary hypoplasia (PH) is defined as defective or incomplete development of lungs that are immature for gestational age. A prospective study was done to establish practical criteria for the diagnosis of pulmonary hypoplasia and to determine the relative frequency of pulmonary hypoplasia and its associated congenital malformations. Postmortem, formalin-inflated, routinely processed lungs were examined for fresh lung weight, fixed lung volume, radial alveolar count, and tissue maturity. Of these, lung volume was found to be the least useful. However, no single parameter was adequate for diagnosis in every case. Using the remaining three in conjunction, reliable diagnostic criteria were established. In this series of 113 cases, 22% had pulmonary hypoplasia as the primary cause of death, of which one-third had no associated congenital malformations to account for the development of pulmonary hypoplasia. It was found that premature rupture of membranes (PROM) for as short as 5 days could lead to fatal PH. It is concluded that PH is a common problem in neonatal autopsies and can be diagnosed in the average laboratory. Recognizing PH is important because once it has developed, intrauterine intervention in cases of oligohydramnios and postnatal treatment with surfactant inhalation cannot influence the outcome. It remains to be seen whether early fluid replacement in PROM will prevent development of PH.Pulmonary hypoplasia (PH) is defined as defective or incomplete development of lungs that are immature for gestational age. A prospective study was done to establish practical criteria for the diagnosis of pulmonary hypoplasia and to determine the relative frequency of pulmonary hypoplasia and its associated congenital malformations. Postmortem, formalin-inflated, routinely processed lungs were examined for fresh lung weight, fixed lung volume, radial alveolar count, and tissue maturity. Of these, lung volume was found to be the least useful. However, no single parameter was adequate for diagnosis in every case. Using the remaining three in conjunction, reliable diagnostic criteria were established. In this series of 113 cases, 22% had pulmonary hypoplasia as the primary cause of death, of which one-third had no associated congenital malformations to account for the development of pulmonary hypoplasia. It was found that premature rupture of membranes (PROM) for as short as 5 days could lead to fatal PH. It is concluded that PH is a common problem in neonatal autopsies and can be diagnosed in the average laboratory. Recognizing PH is important because once it has developed, intrauterine intervention in cases of oligohydramnios and postnatal treatment with surfactant inhalation cannot influence the outcome. It remains to be seen whether early fluid replacement in PROM will prevent development of PH.

Bronchiolitis obliterans organizing pneumonia-like reactions: A nonspecific response or an atypical form of rejection or infection in lung allograft recipients?

Bronchiolitis obliterans organizing pneumonia (BOOP) is a ubiquitous entity, known to occur either idiopathically or in association with various pulmonary disorders. Histologically, it is characterized by myxomatous connective tissue plugs present in the lumen of bronchioles with extension into the alveoli. Its significance in lung allograft recipients is not well documented. The authors reviewed all post-lung transplant biopsies (565 transbronchial; 19 open), explanted lungs for retransplantation (six), and autopsies (38) from 115 patients. A total of 32 patients (18 females and 14 males) showed histological evidence of BOOP-like reactions (ie, Masson bodies in 44 transbronchial and seven open lung biopsies). The mean age was 47 years (range = 14 to 69 years). Sixteen patients were recipients of single lungs, 14 received bilateral single lungs, and two had heart and double-lung transplants. BOOP-like reactions (BOOP-LRs) occurred as early as day 5 and as late as day 1,208 (40 months) posttransplantation. Twenty patients had one biopsy showing BOOP-LR, of which three patients had resolving mild acute rejection, four had ongoing minimal acute rejection, seven had ongoing mild acute rejection, one each had ongoing moderate and bronchiolar rejection, and four showed associated cytomegalovirus (CMV) pneumonitis. Seven patients had two biopsies each of BOOP-LR of which six were associated with ongoing minimal or mild acute rejection, and one had resolving mild acute rejection. Three patients had three biopsies each of BOOP-LR all associated with ongoing minimal or mild acute rejection. Two patients had four biopsies each, showing BOOP-LR, with ongoing mild or moderate acute rejection or CMV pneumonitis. Forty of the total 115 lung transplant patients (34.8%) have developed bronchiolitis obliterans syndrome (BOS) or chronic airway rejection. Twelve of these patients are from the study group, of which five have a biopsy proven histological diagnosis of obliterative bronchiolitis (OB), and the remaining seven patients have been diagnosed clinically by deteriorating lung function tests. The authors conclude that BOOP-LR in the lung transplant setting result from acute epithelial injury secondary to either allograft rejection or an ongoing infection and are not a component of, nor do they necessarily predispose to, chronic rejection.

Mycobacterial DNA in recurrent sarcoidosis in the transplanted lung - A PCR-based study on four cases

Abstractu2002Sarcoidosis is a systemic granulomatous inflammation, which may be caused by mycobacteria other than M. tuberculosis complex (MOTT) in one-third of cases. A few cases of recurrent sarcoidosis in the transplanted lung have been reported. However, mycobacteria have been excluded by acid-fast stains only. We investigated four cases of recurrent sarcoidosis in lung transplant patients. Using PCR for the insertion sequence 6110 of Mycobacterium tuberculosis complex and a second PCR for the mycobacterial chaperonin (65-kDa antigen coding sequence), we looked for mycobacterial DNA. In three cases sequence analysis was also performed. One patient was negative for mycobacterial DNA in explanted, but positive for M. tuberculosis DNA in transplanted lung, qualifying this case as M. tuberculosis infection in the transplant. Three patients were negative for M. tuberculosis DNA, but were positive for MOTT-DNA in both explanted and transplanted lungs. In these three patients sequence identity of the amplified sequences before and after transplantation was proven, which rules out mycobacteriosis. Recurrent sarcoidosis does occur, but can only be proven by the exclusion of mycobacterial DNA. In cases of recurrent MOTT-DNA-positive sarcoidosis the diagnosis cannot be confirmed except by proof of sequence identity. Probably MOTT-DNA-positive sarcoidosis is more likely to recur in a transplanted lung.

Quantification of cytomegalovirus (CMV) viral load by the hybrid capture assay allows for early detection of CMV disease in lung transplant recipients

BACKGROUNDnWe prospectively compared the hybrid capture system (HCS) assay with conventional cell culture and shell vial assay for the detection of cytomegalovirus (CMV) infection and disease in the lung transplant population.nnnMETHODSnBetween January 1999 and February 2000, 34 lung transplant patients at Loyola University Medical Center, who were considered to be at risk for CMV disease, underwent surveillance testing for CMV cell culture, shell vial assay and HCS assay according to a pre-determined schedule. In addition, bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy were performed at regular intervals and for clinical indications. All BAL samples were sent for CMV cultures and biopsy specimens were analyzed for histopathologic evidence of CMV by immunoperoxidase staining using antibody to early immediate nuclear antigen.nnnRESULTSnTen patients developed CMV disease/syndrome during the course of the study. The sensitivity, specificity, positive predictive value and negative predictive value were >90% for the HCS assay. The sensitivity of the HCS assay (90%) was statistically significantly higher than the sensitivity of either the SV assay (40%) or the cell culture (50%). In addition, the HCS assay was able to detect CMV 50 +/- 67 days prior to clinical evidence of CMV disease and an average of 36 days prior to the other detection techniques.nnnCONCLUSIONnThe HCS assay is a sensitive diagnostic technique able to reliably detect CMV disease earlier than other diagnostic methods in the lung transplant population. Future studies may be able to evaluate whether pre-emptive anti-viral therapy targeted to specific viral loads using the HCS assay will be beneficial in preventing morbidity associated with CMV disease.

Segmental Absence of Small Intestinal Musculature

Three instances of segmental absence of small intestinal musculature are described. Based on their clinical and pathological features and on the 12 cases previously described in the English literature, these can be classified into two groups: primary and secondary. In the primary group, the etiology is unknown, the onset of symptoms is acute, and there are no pathologic findings in the remaining layers of the small bowel except for superimposed perforation, or intussusception. In the secondary group, there is a longer history of intestinal symptoms and of multiple surgical procedures. Histologically, there may be ischemic necrosis of remaining layers, fibrosis, calcification, chronic inflammation, and presence of macrophages. These findings indicate secondary destruction of muscle layers due to ischemia and/or infarction, interruption of the blood supply, or trauma.

Synchronous adenocarcinoma and carcinoid of the uterine cervix: Immunohistochemical study of a case and review of literature

Mixed neoplasms, adenocarcinoma and carcinoid, have been reported to occur in several areas of the body, including gastrointestinal tract, breast, prostate, lung, skin, and kidney. Mixed tumors of the uterine cervix are very rare. Their histogenesis, immunohistochemical profile, and prognosis are not well established. Here, we report a case of a 49-year-old female with infiltrating adenocarcinoma of the cervix within which was found a separate nodule of small cell endocrine carcinoma.

Primary malignant melanoma of the larynx.

Primary malignant melanoma of the larynx is a rare clinical entity. Only 53 cases have been reported in the medical literature to date. This report describes a case of primary malignant melanoma arising in the larynx and diagnosed by histologic examination of an excisional biopsy specimen. The patient was a 53-year-old man with a history of smoking and hoarseness. There was no clinical evidence of other primary malignant melanocytic lesions. Microscopically, the tumor consisted of polygonal-epithelioid cells admixed with more elongated, spindle-shaped cells. The majority of the cells demonstrated dark brown cytoplasmic and nuclear melanin. Marked pleomorphism and abnormal mitoses were also identified. Despite significant ulceration and disruption of the epithelium, in situ malignant melanocytes were recognized within the remaining portion of the epithelium. Immunohistochemical studies were positive for S100, HMB-45, and vimentin, while cytokeratin and iron stains were negative. Based on the clinical and histologic findings, a diagnosis of primary malignant melanoma of the larynx was established.

Parasitic Conjoined Twins with Omphalocele and Tetralogy of Fallot

Human parasitic twins are very rare. Here we report a unique case of a partial twin attached to the host in the midline at the forehead, chin, chest, and epigastrium. The parasite lacked thoracic organs and major neural tube derivatives. However, it had small peripheral nerves and ganglia within perirenal and pericolonic connective tissue. Also present were a well-developed small intestine, colon, and appendix with normal submucosal and myenteric plexuses. These findings may represent either the initial presence of a neural tube that later regressed or migration of autosite neural crest cells. The parasite had a mature, functioning kidney with its ureter opening to skin and complete absence of urinary bladder or genital organs. This raises questions about the embryological development of the ureteric bud, which is an outgrowth of the mesonephric duct. The host had tetralogy of Fallot and omphalocele containing the parasitic kidney and bowel. Parasitic twinning occurs at 3 weeks of gestation, tetralogy of Fallot at 3-7 weeks, and omphalocele at 6-10 weeks. A single noxa acting at 3 weeks could have caused sequential malformations that initially seem unrelated.