Three-dimensional power Doppler ultrasound for the study of cervical cancer and precancerous lesions.

OBJECTIVE: To evaluate the blood flow characteristics of the cervix in normal women and in women with cervical precancerous lesions or cervical cancer. METHODS: We studied 165 women with three-dimensional power Doppler ultrasound (3D-PDU), of whom 71 had cervical cancer, 61 had precancerous lesions and 33 were healthy controls. The cervix was manually traced in the stored volumes using 15° rotation steps and the following 3D-PDU indices were calculated: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). These indices were compared among the study groups and were also correlated with features of the precancerous lesions group and cancer group. RESULTS: The three indices were all statistically significantly higher in the cervical cancer group and precancerous lesions group than in controls (P < 0.001). In addition, significantly higher values of all indices were found in the cervical cancer group than in the precancerous lesions group (P < 0.001). Further analysis according to patient characteristics in the cancer group showed that VI, FI and VFI were not significantly different in relation to grade, histology, presence of positive lymph nodes or lymphovascular space involvement (P > 0.05). However, VI was significantly higher in patients with Stages IIIB-IV cancer than in patients with less advanced disease (P = 0.045). In the cervical cancer group there was a significant positive correlation between 3D-PDU indices and cervical volume. CONCLUSION: 3D-PDU assessment of the cervix reveals significant differences in all indices studied between women with cervical precancerous lesions or cancer and healthy women. In women with cervical cancer, an advanced stage is associated with higher VI, but 3D-PDU indices are not related to other pathological characteristics.

Causes of infertility in men with Down syndrome.

Men with Down syndrome are considered as infertile although the causes of infertility are not known in detail yet. Although this constitutes a general rule there are three confirmed cases of parenting by fathers with Down syndrome. Many investigators have addressed the causes of infertility and their studies indicate that the causes may be hormonal deficits, morphological alterations of the gonads, abnormal spermatogenesis, psychological and social factors related to the mental retardation. It is obvious that the extra chromosome 21 has a detrimental direct and indirect effect on the reproductive capacity of the affected male patient. But the definite cause of the insufficient and inadequate spermatogenesis remains to be discovered.

Cryptosporidiosis in patients with AIDS: correlates of disease and survival.

Although 10%-15% of patients with AIDS in the United States may acquire cryptosporidium infection, little data exist on clinical or histological characteristics that differentiate clinical outcomes. A case-control study of 83 HIV-positive adult patients with cryptosporidiosis was conducted, as was a histopathologic review of data on gastrointestinal biopsy specimens from 30 patients. Four clinical syndromes were identified: chronic diarrhea (36% of patients), choleralike disease (33%), transient diarrhea (15%), and relapsing illness (15%). A multivariate analysis of data for cases and controls revealed that acquiring cryptosporidiosis was associated with the presence of candidal esophagitis (odds ratio [OR], 2.53; P < .002) and Caucasian race (OR, 6.71; P = .0001) but not with sexual orientation. Cases had a significantly shorter duration of survival from the time of diagnosis than did controls (240 vs. 666 days, respectively; P = .0004), which was independent of sex, race, or or injection drug use. Antiretroviral use was protective against disease (OR, 0.072; P = .0001). All four clinical syndromes were represented among the histological data. There was no statistically significant correlation between histological intensity of infection and clinical severity of illness.

A clinicopathologic analysis of AIDS-related cryptosporidiosis.

OBJECTIVE: To characterize the histology of AIDS-associated cryptosporidiosis and identify features that explain the clinical variability. DESIGN: A retrospective analysis of HIV-positive individuals with cryptosporidiosis who underwent endoscopy at the Johns Hopkins Hospital between 1985 and 1996. METHODS: The histologic features (intensity of Cryptosporidium infection, inflammation, mucosal damage, copathogens) of gastrointestinal biopsies from 37 HIV-positive individuals with cryptosporidiosis were systematically graded. These histologic features were correlated with the severity of the diarrheal illness obtained from a patient chart review. RESULTS: Histologic features associated with Cryptosporidium infection include a neutrophilic infiltrate in the stomach, villus blunting in the duodenum, cryptitis and epithelial apoptosis in the colon, and reactive epithelial changes in the stomach and duodenum. The nature and intensity of the inflammatory response varied widely; however, duodenal biopsies from a subset of patients (37%) revealed marked acute inflammation that was associated with concomitant cytomegalovirus infection. Although duodenal infection was common (93% of individuals), infection of other sites was variable (gastric cryptosporidiosis in 40% and colonic cryptosporidiosis in 74%). Widespread infection of the intestinal tract, which included both the large and small intestine, was associated with the most severe diarrheal illness. CONCLUSIONS: Cryptosporidium infection produces histologic evidence of gastrointestinal mucosal injury. The inflammatory response to the infection is variable, and may be modified by copathogens such as cytomegalovirus. The clinical manifestations are influenced, in part, by the anatomic distribution of the infection, with extensive infections involving both small and large intestines producing the most severe illness.

Hepatomegaly and steatosis in HIV-infected patients receiving nucleoside analog antiretroviral therapy.

BACKGROUND: A syndrome of hepatomegaly with severe steatosis has been described in case reports and case series in HIV-infected patients receiving nucleoside analog antiretroviral therapy. We wished to quantitate the incidence of this syndrome in a well characterized, demographically heterogeneous cohort of HIV-infected patients followed longitudinally. METHODS: All patients enrolled into a comprehensive primary care HIV Clinic from July 1989 through July 1994 (N = 1836) were screened for evidence of steatosis and liver disease by assessment of hospital discharge diagnoses, pathology reports, out- and in-patient laboratory data, and clinic records. RESULTS: A total of 322 (18%) patients had evidence of a liver abnormality. In these patients, viral hepatitis and alcohol-induced liver disease were the most common diagnoses. Only two patients had hepatomegaly with moderate to severe steatosis and acidosis. Both cases occurred in white men with very advanced HIV disease who were receiving nucleoside analog antiretroviral therapy. The incidence of the syndrome was 1.3 per 1000 person-yr of follow-up in antiretroviral users in our cohort (95% confidence interval: 0.2, 4.5 per 1000 person-yr). CONCLUSION: The hepatic steatosis syndrome manifesting as a severe, potentially fatal complication of antiretroviral therapy in HIV disease is rare. Both men and women and patients in early and late stages of HIV infection appear to be susceptible. It is not currently known whether a milder form of this syndrome is occurring in a larger population.

Management of HIV-associated esophageal disease.

AIDS: Esophageal conditions due to fungal, ulcerative, and neoplastic causes often signal the onset of symptomatic HIV infection. Most cases are fungal and due to Candida albicans, which is characterized by esophageal inflammation causing pain on swallowing (dysphagia and odynophagia). Ulcerative esophageal disease is commonly associated with cytomegalovirus (CMV), idiopathic causes, and herpes simplex virus (HSV). CMV, characterized by odynophagia resulting from ulcerations in the distal third of the esophagus, is clinically indistinguishable from idiopathic ulceration. HSV is more widespread and abrupt than other ulcerative processes, and its erosive injury can cause painful swallowing, ulceration and oral cavity lesions. Patients with esophageal distress, low CD4 counts, and little possibility of other GI conditions most likely suffer from Candida infection and should immediately begin an empiric trial of antifungal therapy. If an individual's first bout of odynophagia does not respond to empiric oral azole therapy, the diagnosis of fungal esophagitis is probably incorrect and an upper endoscopic evaluation should be performed. Patients generally respond quickly and completely to treatment of a first episode of fungal esophagitis; therefore, neither primary prophylaxis nor long-term suppressive therapy are recommended due to the risk of infection with a resistant strain. Failure of patients on suppressive therapy to respond to antifungal medication usually indicates resistant fungal infection that may require treatment with intravenous amphotericin. If CMV-isolated esophagitis is diagnosed, the patient should begin intravenous ganciclovir, followed by IV foscarnet if the healing after three weeks is minimal.^ieng

AIDS enteropathy.

Chronic diarrhea is one of the hallmarks of advanced human immunodeficiency virus (HIV) disease. The symptoms of this complication are troublesome, have a significant impact on the patient's quality of life, and in severe cases can lead to extreme abnormalities in fluids and electrolytes and can even cause death. The workup for AIDS-associated diarrhea is often frustrating and frequently unrewarding. However, during the last 10 years, much has been learned about the causes of diarrhea; while treatment is still often ineffective, some advances have been made. Dr. John G. Bartlett and his colleagues in the Department of Medicine at Johns Hopkins University School of Medicine have been responsible for many of these advances. In this AIDS Commentary, these experts discuss recent advances that have enhanced our understanding of chronic diarrhea in HIV-infected persons and offer their recommendations for the most efficient and effective approach to managing these patients.

Association of gastric hypoacidity with opportunistic enteric infections in patients with AIDS.

To determine the relation and possible significance of gastric hypoaciditity to chronic diarrhea in AIDS, patients with and without chronic (greater than 1 month) diarrhea underwent fasting gastric juice pH measurement and microbiologic study and upper and lower endoscopy with biopsy. All 8 patients with diarrhea and high gastric pH (greater than 3; mean, 6.1 +/- 1.0) had gastric bacterial overgrowth (greater than 10(4) bacteria/mL) along with opportunistic enteropathogens in the duodenum or rectosigmoid, but only 1 of 6 patients with diarrhea and gastric pH in the normal range (less than or equal to 3; mean, 1.9 +/- 0.7) had overgrowth or an opportunistic enteropathogen. By contrast, all but 1 of 9 controls (AIDS patients without diarrhea) had normal fasting gastric pH (mean, 2.9 +/- 1.5). Overall, the presence of gastric hypoacidity was associated with identification of opportunistic enteropathogens (P = .035). Thus, gastric hypoacidity is associated with quantitative bacterial overgrowth and opportunistic enteric infections and may be etiologically important in the pathophysiology of the chronic diarrhea seen in some AIDS patients.

Intestinal injury associated with spiramycin therapy of Cryptosporidium infection in AIDS.

Two of three patients treated with high doses of spiramycin for Cryptosporidium infection developed acute intestinal injury. Spiramycin at high doses may be directly toxic to the intestinal epithelium and thus may have limited utility as therapy for cryptosporidiosis in AIDS patients.

AIDS enteropathy: occult enteric infections and duodenal mucosal alterations in chronic diarrhea.

OBJECTIVE: To investigate occult enteric infections and morphologic changes in the small intestine in patients with advanced human immunodeficiency virus (HIV) infection and chronic diarrhea of undefined cause. DESIGN: Case-control study. SETTING: Referral-based clinic and hospital in tertiary care center. PATIENTS: Twenty-two patients with advanced HIV infection (19 with the acquired immunodeficiency syndrome [AIDS], 3 with AIDS-related complex) with chronic diarrhea, selected because of previously negative stool evaluations for bacterial or parasitic pathogens, were compared with 13 patients with advanced HIV infection (9 with AIDS, 4 with AIDS-related complex) without diarrhea by analysis of endoscopic biopsies using light and electron microscopy, viral culture, and morphometric studies. Both groups were convenience samples and had at least 7 months follow-up. MEASUREMENTS AND MAIN RESULTS: Eleven of twenty-two patients with HIV infection and chronic diarrhea but only 1 of 13 patients without diarrhea showed occult enteric pathogens (that is, undetected by routine studies) after extensive evaluation of duodenal and colorectal biopsies. Mycobacterium avium-intracellulare and microsporidia were the most common occult agents in study patients with diarrhea (5 each). Patients with diarrhea and occult enteric infections had greater weight loss (mean, 14.3 kg compared with 6.2 kg; P less than 0.05) and shorter survival (1 of 11 compared with 8 of 11 still alive; P less than 0.004) than those with diarrhea but no identified pathogens (defined as "AIDS enteropathy"). Duodenal morphometry showed decreased villus-to-crypt ratios because of villus atrophy and crypt elongation in HIV-infected patients both with and without diarrhea compared with normal controls (P less than 0.001 for each). All three groups showed comparable frequencies of epithelial mitoses. CONCLUSIONS: Further endoscopic biopsy evaluation of patients with AIDS who had unexplained chronic diarrhea showed an occult infectious cause in half of the cases. However, altered villus and crypt architecture in advanced HIV infection was independent of the presence of diarrhea or enteric infection and therefore did not correlate with AIDS enteropathy. Subnormal epithelial proliferation in response to injury could be a factor, but the underlying cause of the architectural changes remains obscure. We suggest that T-cell dysfunction may play a role.

Homotypic cell aggregation induced by anti-CD44(Pgp-1) monoclonal antibodies and related to CD44(Pgp-1) expression.

The present study shows that a mAb (H4C4) developed against human peripheral blood adherent cells has the unusual property of inducing in vitro homotypic aggregation of several types of hemopoietic cells and cell lines. The Ag recognized by mAb H4C4 is a 85-kDa glycoprotein that corresponds to the human Ag CD44 (equivalent to murine Pgp-1), as determined by protein purification, immunologic cross-reactivity studies, and tryptic fragment sequencing. In addition to H4C4, other mAb directed against some, but not all, epitopes of CD44(Pgp-1) were capable of inducing cell aggregation. This process was temperature sensitive and was almost totally abrogated by cytochalasin B but was unaffected by sodium azide, colchicine, EGTA, trifluoperazine, or staurosporin. A role for CD44 (Pgp-1) in cell-to-cell adhesion was further indicated by an inverse relationship observed between spontaneous aggregation of some hemopoietic cell lines and cell-surface expression of CD44(Pgp-1). These observations provide evidence for a fundamental role of CD44(Pgp-1) in cellular aggregation phenomena with an involvement of the cytoskeleton.

Strategies for increasing house staff management of cholesterol with inpatients.

This study tested the effectiveness of two conceptually different chart audit-based approaches to modifying physicians' clinical practices to conform with quality-assurance standards. The objective was to increase intern utilization of cholesterol management opportunities in the inpatient setting. Using a clinical trial study design, 29 internal medicine interns were randomly assigned to four intervention groups identified by the intervention they received: control, reminder checklists (checklists), patient-specific feedback (feedback), or both interventions (combined). Over a nine-month period, intern management of high blood cholesterol levels in internal medicine inpatients (n = 459) was monitored by postdischarge chart audit. During both a baseline and subsequent intervention period, interns documented significantly more cholesterol management for inpatients with coronary artery disease (CAD) than without CAD. During baseline, 27.3%, 24.3%, 21.7%, 12.4%, 5.4%, and 2.7% of all inpatient charts had intern documentation concerning a low-fat hospital diet, cholesterol history, screening blood cholesterol level assessment, follow-up lipid profile, nutritionist consult, and preventive cardiology consult, respectively. The feedback intervention significantly increased overall intern-documented cholesterol management among inpatients with CAD. The checklists significantly decreased overall intern-documented cholesterol management. Feedback appears to be an effective approach to increasing intern cholesterol management in inpatients.