Faculty Bibliography

This compassionate-use study examined the efficacy of foscarnet in patients with AIDS and cytomegalovirus (CMV) gastrointestinal disease who had failed ganciclovir induction. Nineteen male homosexuals with AIDS and biopsy-proven CMV gastrointestinal disease who had twice failed standard ganciclovir induction (defined as progression of clinical CMV disease) were studied. Foscarnet 60 mg/kg every 8 h was administered intravenously for 14 days, then maintenance was utilized at 90 or 120 mg/kg every day with 1 L normal saline daily. Endpoints included endoscopic appearance, blinded histopathologic analysis of biopsies for CMV inclusions, and changes in symptoms by 50% from baseline. Patients were evaluated before and 2-3 wk after foscarnet. Histopathologic improvement was seen in 67%, whereas 74% improved clinically after a median duration of 7.5 days (1-12). Among the nine with esophageal disease, six patients (68%) had a clinical response and six of eight (75%) had a pathologic response. Among the 10 with colonic disease, eight patients (80%) had a clinical response and six (60%) had a pathologic response. Reversible elevations in creatinine were seen in two of 17 (12%). Three patients with esophageal disease developed strictures late in therapy requiring dilation. Median survival after foscarnet induction was 5.0 months. Foscarnet appears to induce remission of CMV gastrointestinal disease in 67% of patients when ganciclovir induction has failed. Reversible nephrotoxicity occurred in 12%. Strictures may be a late complication of CMV esophagitis

The efficacy and safety of ganciclovir therapy for cytomegalovirus (CMV) colitis in patients with AIDS was examined in a double-blind, placebo-controlled study. Sixty-two patients at four university medical centers were enrolled. All had biopsy-proven CMV colitis with diarrhea, fever, and weight loss. Other pathogens were excluded. Ganciclovir (5 mg/kg) or placebo was administered every 12 h for 14 days. A significant reduction in CMV-positive colonic and urine cultures was seen with ganciclovir (P = .034 and P < .001, respectively) compared with placebo. Colonoscopy scores were improved significantly more with ganciclovir than with placebo (P = .042). New extracolonic CMV disease developed in 7 (23%) of 30 placebo patients and in 3 (9%) of 32 ganciclovir patients in only 14 days (P = .026). Ganciclovir-treated patients maintained body weight, while placebo patients had a mean loss of 1.5 kg. Overall, ganciclovir appears of some benefit in treating CMV colitis in patients with AIDS

Extrapulmonary infection with Pneumocystis carinii in AIDS patients on aerosolized pentamidine is occurring more frequently. We report five patients diagnosed with gastrointestinal pneumocystosis while on aerosolized pentamidine prophylaxis and have identified infections involving the peritoneum, liver, and transverse colon, as well as stomach and duodenum. Physicians should have a high index of suspicion for extrapulmonary pneumocystosis, especially involving the gastrointestinal system, in HIV-infected patients, and early diagnosis must be pursued aggressively. The use of aerosolized pentamidine as prophylaxis for P. carinii pneumonia is not protective against gastrointestinal pneumocystosis because of inadequate systemic distribution of the drug. To our knowledge, this is the first report in a clinical journal documenting and photographing P. carinii organisms in ascitic fluid

Kaposi's sarcoma (KS) is the most common tumor among HIV-infected individuals, but its involvement in the gastrointestinal tract was reported long before the AIDS epidemic. Although most cases of gastrointestinal KS are asymptomatic, advanced lesions may occasionally result in a severe and life-threatening hemorrhage that requires immediate treatment. At the NYU Medical Center, we have seen three AIDS patients present with severe upper tract bleeding (> 8 U/48 h) from KS lesions of the antrum, fundus, and duodenum. The last patient was also bleeding from an ulcerated rectal KS lesion. Because all three patients had a coexisting thrombocytopenia (platelets < 50,000/mm3) and were poor operative risks, injection sclerotherapy was performed. All four KS lesions stopped bleeding, and three out of the four lesions decreased in size. To our knowledge, this is the first report of successfully using sclerotherapy to treat severe hemorrhage due to gastrointestinal KS

OBJECTIVE: Primarily to determine whether an intestinal microsporidian recently identified in AIDS patients disseminates from the bowel to infect other organs. DESIGN: Disseminated microsporidiosis has been reported in immunocompromised humans, but never due to Enterocytozoon bieneusi, the most common species in AIDS patients and one that evidently infects only enterocytes. In animals, dissemination follows ingestion of Encephalitozoon cuniculi spores, apparently via macrophages, and pathology occurs in, for example, kidneys and brain. A second, un-named Encephalitozoon-like intestinal microsporidia has been identified in five AIDS patients with chronic diarrhea; because it infects lamina propria macrophages, it was logical to investigate its dissemination. METHODS: Light and transmission electron microscopy were used to study urine sediment from four out of five patients with biopsy-documented small intestinal infection due to the second intestinal microsporidian. The gall bladder from one patient and autopsy specimens from an E. bieneusi-infected patient were similarly studied. RESULTS: Systemic dissemination was documented by detecting abundant spores, both free and within renal tubular and transitional cells, in the urine of two patients. Many of the lamina propria macrophages in these two patients' intestinal biopsies contained microsporidia, while those of the two negative patients either contained only Mycobacterium avium complex or only occasional parasites. The gall bladder was co-infected with this microspordian and with cytomegalovirus. At autopsy, the patient with documented enteritis due to E. bieneusi 2 years before death had disseminated microsporidiosis, not of E. bieneusi, but apparently of the second intestinal species. The microsporidian had caused severe tubulointerstitial nephritis. Parasites were also observed in non-parenchymal cells of the liver and bronchial epithelium. CONCLUSION: A newly described Encephalitozoon-like intestinal microsporidian, which causes chronic diarrhea in AIDS patients, can disseminate and cause renal pathology

OBJECTIVE: To detect and quantify HIV-1 in the liver in vivo. DESIGN: Fourteen liver biopsy samples and corresponding blood lymphocytes and monocytes from patients with AIDS were studied for HIV-1 using quantitative polymerase chain reaction (PCR). In addition, expression of HIV-1 antigen and messenger (m) RNA in 10 autopsy liver specimens was examined by immunohistochemistry and in situ hybridization. RESULTS: The amount of HIV-1 DNA in nine liver samples ranged from 850 to 27,000 copies per 10(6) cells, with mean and median values of 8150 and 3500 copies per 10(6) cells, respectively. Five other samples had no detectable HIV-1 DNA by PCR. Intracellular expression of HIV-1 antigen and mRNA was also detected in both Kupffer cells and hepatocytes by in situ studies. CONCLUSION: These findings strongly indicate that HIV-1 could replicate in the liver of a majority of patients with AIDS

We have reviewed 28 esophageal biopsies from 28 patients with the acquired immune deficiency syndrome (AIDS), over a 1-yr period. Indications for esophageal biopsy were dysphagia persisting after antifungal therapy and/or radiologic evidence of esophageal ulcer. We compared the frequency of detecting cytomegalovirus (CMV) infection on hematoxylin and eosin (H&E) stain with immunoperoxidase staining for CMV antigens. Five biopsies were positive for CMV by H&E stain and immunoperoxidase. Infected cells could often be identified in the granulation tissue and, in one severe case, in stromal papillae of the intact mucosa. Squamous cells were never positive. Thirteen biopsies consisted only of squamous epithelium, and all of these were negative by both techniques. Among the remaining 10 cases, no CMV inclusions were identified by H&E. Three of these biopsies displayed staining for viral antigens. In all cases positive by immunoperoxidase, numerous cells positive for viral antigens did not display any of the CMV-specific morphologic diagnostic criteria. Other coexisting diagnoses included candidiasis, Kaposi's sarcoma, and malignant lymphoma. We conclude 1) CMV infection of the esophagus is common in AIDS patients with esophageal ulcer or esophagitis resistant to antifungal therapy; 2) multiple infections or neoplasms may coexist; 3) since CMV apparently does not infect squamous epithelium and only rarely endothelium in stromal papillae, deep biopsies are necessary for diagnosis; and 4) immunoperoxidase staining is required for maximum diagnostic yield

We report a homosexual patient with the acquired immune deficiency syndrome (AIDS) and histopathologic evidence for cytomegalovirus (CMV) appendicitis in a patient with no prior history of CMV infection. The patient presented with right lower quadrant pain and intermittent fevers. The diagnosis of appendicitis was difficult to make in this patient because of the presumptive diagnosis of tuberculosis ileitis and the frequent presentation of abdominal pain with fever in AIDS patients. Although CMV colitis is frequently seen in AIDS patients, the prevalence of CMV appendicitis is exceedingly rare. The problems related to making a diagnosis of CMV appendicitis and the therapeutic management of CMV infections are reviewed