Biomedical subjects
Publications and source records attributed to M Ho.
Intra-abdominal actinomycosis is rarely suspected and is difficult to diagnose. A 46-year-old woman with intra-abdominal actinomycosis is described in whom the condition was first suspected when sulfur granules were found in her urine. The infection had involved her bladder but not her kidneys.
A monoclonal diffuse histiocytic lymphoma developed during the course of a serologically documented primary Epstein-Barr virus infection in a 22-year-old cardiac transplant recipient taking cyclosporine and prednisone. Throat washings revealed the virus at tumor presentation, and the tumor was shown to contain Epstein-Barr nuclear antigen-positive cells and the viral genome. Prolonged inversion of the T cell helper/suppressor ratio was demonstrated. A brief course of acyclovir appeared to halt viral shedding in the throat but had no apparent effect on the tumor.
The roles of vitamin D, calcitonin, and parathyroid hormone in calcium metabolism during lactation may be more evident in women secreting very large amounts of milk for a number of months, as in mothers nursing twins. We report significant increases in serum concentrations of parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D in mothers nursing twins compared to mothers nursing single infants. Serum concentrations of calcium actually increased in both groups during lactation. Maternal intakes of calories, calcium, and phosphorus were significantly higher in mothers nursing twins. Thus, mothers nursing twins were able to compensate for higher calcium losses in breast milk by increased dietary intakes of calcium as well as increased serum concentrations of parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D.
Fourteen of 156 renal-transplant recipients treated with cyclosporine and steroids developed Pneumocystis carinii-related pneumonia (PCP) over a 19-month period. This was a significant change from past experience with this disease in renal-transplant patients receiving azathioprine and steroids (six cases among 179 patients from 1977 to 1981). Epidemiological investigation failed to implicate either person-to-person or nosocomial spread of infection. Cases of PCP occurred more frequently in males. Twelve patients (86%) had onset of disease in the third or fourth months after transplantation. Comparison of cases to matched controls revealed that the cases had received lower doses of steroids and had a higher incidence of cytomegalovirus infection. This suggested that the cases may have been more effectively immunosuppressed than the controls. After institution of prophylaxis with trimethoprim-sulfamethoxazole, no further cases of PCP developed.
Fifty-five patients undergoing microvascular decompression for trigeminal neuralgia were divided into three groups in a two-stage placebo-controlled study. All groups received two injections a day for five days beginning the day before surgery. Twenty-one patients received 10 placebo injections, 11 in the presurgical treatment group received three injections of 3.5 X 10(4) units of leukocyte interferon/kg before surgery, and 23 in the postsurgical treatment group received seven injections after surgery. The remaining injections in the two treatment groups were placebos. In the first stage, with 30 patients, 91% of the presurgical treatment group had reactivated oral herpesvirus infections (manifested by herpetic lesions and/or oral viral shedding) significantly more often than did concurrent controls (P less than .05). In the second stage, only the postsurgical treatment and placebo groups were studied, with no difference in reactivation of herpesvirus infection between the postsurgical treatment and placebo groups. Thus presurgical treatment with interferon alone may actually precipitate and accentuate herpesvirus infection.
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Acute CMV infection in the mouse results in depressed antibody production, IFN induction, lymphocyte proliferation responses to mitogens, allogeneic skin graft rejection, and clearance of certain bacteria and fungi from the blood stream. CMV mononucleosis in humans is associated with decreased lymphocyte proliferation responses to mitogens and herpesvirus antigens, decreased IFN production, and reversal of the T-helper to suppressor cell ratio. In recent studies, we have shown that NK activity is depressed after renal transplantation and the use of cyA, and is poorly enhanced by the addition of IFN to in vitro assays. In vitro induction of alpha-IFN as well as gamma-IFN by NDV and enterotoxin-A is also inhibited. These deficits may contribute to the severity of CMV infections in this patient population.
Plasma concentrations of 25-hydroxy- and 1,25-dihydroxyvitamin D in chronically catheterized fetal and maternal sheep preparations and transfer of 3H-1,25-(OH)2-D3 from the fetus to mother and vice versa were studied. We tested the hypothesis that 1,25-(OH)2-D does not cross the placenta in either direction. While the fetal plasma 25-(OH)-D concentration was lower than the corresponding maternal values (n = 9, p less than 0.02), the fetal 1,25-(OH)2-D concentration was higher than the mother's (n = 9, p less than 0.02). 3H-1,25-(OH)2-D3 crossed the placenta from the fetus to the mother (n = 4) and vice versa (n = 4). We speculate, therefore, that maternal vitamin D metabolism may be affected by fetal vitamin D metabolism through the transplacental crossover of its highly active metabolite.
The natural history of genital herpes simplex virus (HSV) infections was investigated in 83 pregnancies in 78 women, and the information was used to determine the need for cesarean section in these women. We studied 163 recurrent episodes with HSV cultures from the cervix and from vulvar lesions every 1 to 3 days. Cervical HSV cultures were obtained weekly from asymptomatic women beginning at 32 weeks' gestation, and 14/462 (3.03%) of these cultures were positive. Cervical cultures obtained during culture-positive vulvar recurrences demonstrated concomitant cervical HSV shedding in 25/165 (15.2%) cultures. Mean duration of 26 genital HSV recurrences was 4.6 +/- 2.8 days with a range of 1 to 13 days. The mean interval between culture-positive HSV recurrences was 59.2 +/- 42.1 days, but many (14/76 = 18%) intervals were less than 21 days. Viral cultures were already positive in 92.3% of cases after 4 days' incubation, so they could be used effectively to determine route of delivery. Following a cautious set of criteria for vaginal delivery in these women, 69.1% were delivered of their infants vaginally and no neonatal morbidity caused by HSV was encountered. Information about the natural history of genital HSV infections obtained from frequent third-trimester viral cultures can be used to manage pregnancy and will reduce the need for cesarean section while avoiding neonatal HSV morbidity.
Human sera from Lodwar (77 sera), Nzoia (841 sera), Masinga (251 sera), Laisamis (174 sera) and the Malindi/Kilifi area (556 sera) in Kenya were tested by indirect immunofluorescence for antibodies against Marburg, Ebola (Zaire and Sudan strains), Congo haemorrhagic fever, Rift Valley fever and Lassa viruses. Antibodies against Ebola virus, particularly the Zaire strain, were detected in all regions and were, over-all, more abundant than antibodies against the other antigens. Ebola and Marburg antibody prevalence rates were highest in the samples from Lodwar and Laisamis, both semi-desert areas. Antibodies against Rift Valley fever virus were also highest in the Lodwar sample followed by Malindi/Kilifi and Laisamis. Congo haemorrhagic fever virus antibodies were rare and no antibodies against Lassa virus were detected in the 1899 sera tested.
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A prospective randomized trial of three dosage regimens of sodium stibogluconate (Pentostam; Wellcome Foundation, London) to treat visceral leishmaniasis was conducted. Previously untreated patients were randomized to receive 31 doses of sodium stibogluconate (10 mg Sb/kg of body weight per dose) administered once daily for 31 days (group A), every 12 hr for 15 days (group B), or every 8 hr for 10 days (group C). Of the 29 patients who completed treatment, seven of 10 in group B and all of the patients in groups A and C responded to treatment and remained well for one year. One patient in group B failed to respond to treatment, and two others in group B initially responded to treatment but relapsed six weeks after discharge. None of the treatment regimens was toxic. Parasites disappeared from splenic aspirates most quickly and hemoglobin levels rose most rapidly in patients receiving sodium stibogluconate every 8 hr. Treatment of visceral leishmaniasis in Kenya with sodium stibogluconate at a dose of 10 mg Sb/kg every 8 hr for 10 days appears to be a safe alternative to conventional treatment. Its efficacy should be confirmed in a larger number of patients.
Eighty-one renal, seventeen heart, and twenty-four liver transplant patients were followed for infection. Seventeen renal patients received azathioprine (Aza) and prednisone as part of a randomized trial of immunosuppression with 21 cyclosporine-and-prednisone-treated renal transplant patients. All others received cyclosporine and prednisone. The randomized Aza patients had more overall infections (P less than 0.05) and more nonviral infections (P less than 0.02) than the randomized cyclosporine patients. Heart and liver patients had more infections than cyclosporine renal patients but fewer infections than the Aza renal patients. There were no infectious deaths in renal transplant patients on cyclosporine or Aza, but infection played a major role in 3 out of 6 cardiac transplant deaths and in 8 out of 9 liver transplant deaths. Renal patients on cyclosporine had the fewest bacteremias. Analysis of site of infection showed a preponderance of abdominal infections in liver patients, intrathoracic infections in heart patients, and urinary tract infections in renal patients. Pulmonary infections were less common in cyclosporine-treated renal patients than in Aza-treated patients (P less than 0.05). Aza patients had significantly more staphylococcal infections than all other transplant groups (P less than 0.005), and systemic fungal infections occurred only in the liver transplant group. Cytomegalovirus (CMV) shedding or serological rises in antibody titer, or both occurred in 78% of cyclosporine patients and 76% of Aza patients. Of the cyclosporine patients, 15% had symptoms related to CMV infection. Serological evidence for Epstein Barr Virus infection was found in 20% of 65 cyclosporine patients studied. Three had associated symptoms, and one developed a lymphoma.
Herpes simplex virus type 1 strains isolated from patients who had received interferon in a clinical trial were not more resistant to human leukocyte interferon than strains derived from recipients of a placebo. The susceptibility of herpes simplex virus type 2 strains isolated from herpes genitalis was slightly less than that of herpes simplex virus type 1 strains causing herpes genitalis.
Nineteen renal transplant recipients receiving cyclosporin A and prednisone, eight kidney recipients receiving azathioprine and prednisone, and 12 healthy volunteers were immunized with 0.5 ml of trivalent influenza vaccine containing A/Bangkok/1/79 (H(3)N(2)), A/Brazil/11/78 (H(1)N(1)), and B/Singapore/222/79. Nine patients (47%) in the cyclosporin A group and five (63%) in the azathioprine group showed fourfold rises in titer to at least one virus strain compared with 12 (100%) in the control group.
Cell-mediated immunity in seven patients with cytomegalovirus mononucleosis was assessed by monoclonal antibody to lymphocyte subsets, lymphocyte blastogenesis, and natural killer cell activity. The patients had decreased ratios of helper (Leu 3a) to suppressor-cytotoxic (Leu 2a) T cells as compared with normal donors. Leu 2a+ T cells from the patients were uniquely sensitive to overnight culturing, which resulted in a 2.6-fold increase in the helper/suppressor cell ratio and the appearance of an unusual third Leu 1+ 2a- 3a- T cell subset. This correlated directly with enhanced blastogenesis to concanavalin A after preculture. Base-line and interferon-boosted natural killer cell responses versus K562 cell targets during cytomegalovirus mononucleosis did not differ from those of normal donors. This suggests that certain cellular immune functions are depressed during cytomegalovirus mononucleosis in correlation with the emergence of a culture-sensitive subset of suppressor T cells. In contrast, cytotoxic lymphocytes appear to function normally and may aid in the resolution of the illness.
Normal subjects (n = 11) had a mean circulating natural killer (NK) cell activity of 188 lytic units per 10(7) peripheral mononuclear blood leukocytes. This activity was significantly enhanced by in vitro incubation with 500 U of alpha-interferon (+207 lytic units). The mean NK activity of renal transplant recipients on azathioprine (n = 17) or on cyclosporine (n = 17) studied at various times after transplantation was significantly decreased, as was the ability of interferon to enhance NK activity. In the cyclosporine group, interferon could not enhance NK titers 1 to 6 weeks after transplantation when the patients were on the highest doses of cyclosporine (mean, 1,002 mg/day) or when they were viremic for cytomegalovirus. After 18 weeks, when the patients received 546 mg/day or when viremia was no longer detected, the ability of interferon to enhance NK activity was more normal. Cyclosporine and cytomegalovirus infection may have a greater effect on the action of interferon on NK activity than on the NK titer per se. This defect may diminish the reserve of NK cells and contribute to post-transplant immunosuppression.