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Data on 49 allogeneic bone marrow transplant (BMT) recipients who developed interstitial pneumonia due to cytomegalovirus (CMV) were collected retrospectively. All patients were treated with ganciclovir and high doses of intravenous immune globulin, although types of immune globulins and schedules of treatment varied. Seventeen (35%) of 49 patients responded to treatment. Thirty days after the diagnosis of interstitial pneumonia, the survival rate among patients was 31%. CMV was detected in 81% of patients on whom autopsies were performed. The survival rate among patients who received total body irradiation (TBI) was significantly lower (11 [27%] of 41) than that among patients who did not receive TBI (six [75%] of eight; odds ratio = 12.3; P = .009). No other factor, including age, grade of graft-versus-host disease, types and dose of immune globulin used, or dose of ganciclovir, was correlated to survival. These results show that although survival of allogeneic BMT recipients with CMV interstitial pneumonia has improved, more than one-half of the patients still died of pneumonia. Thus, both prophylaxis for and treatment of CMV infection must be improved.

An outbreak of pharyngitis due to group A beta-hemolytic streptococci type T 12 occurred at a military base. An epidemiologic investigation indicated that the outbreak was food borne. Consumption of boiled egg salad at lunch was significantly associated with the illness. Immediate institution of antibiotic therapy and isolation of the patients prevented secondary respiratory spread of the infection. No cases of poststreptococcal suppurative and nonsuppurative complications were found during a 6-week period after the outbreak. Medical personnel should be aware of the possibility of food-borne streptococcal pharyngitis. Regular health surveillance of food handlers and food preparation processes are important for prevention of such outbreaks.

Following a small outbreak of poliomyelitis which occurred in the summer of 1988 in Israel, two sequential doses of inactivated polio vaccine (IPV) were administered to 42 bone marrow transplant (BMT) recipients (aged 2-50 years) who were 6-96 months (median 16 months) after transplantation. Prior to vaccination, only 68-80% patients (n = 42) had protective (greater than or equal to 4) antibody levels against the three serotypes of poliovirus, compared with 92-96% (n = 25) before BMT (p = 0.02 for types 1 and 3). After the second dose of IPV, 89-98% (n = 27) of the recipients had protective antibody levels. The pre-vaccination antibody titers were lower than before BMT (p = 0.006, 0.0007 and 0.0008 for types 1,2 and 3, respectively). After the first dose of IPV, antibody titers rose in the 42 patients (p = 0.002, 0.043 and 0.002 for types 1, 2 and 3, respectively) and following the second dose, a further increase in antibody levels was noted. Regression analysis revealed that graft-versus-host disease, pre-BMT polio antibody titers, age and type of transplantation (allogeneic versus autologous) were significant explanatory variables for the specific antibody levels, while the time lapse between BMT and vaccination, and primary disease proved of no significance. Vaccination against poliovirus after BMT is advocated, as it reinstates and raises the lost specific humoral immunity.

Occurrence and significance of specific IgA and IgM to cytomegalovirus (CMV) in recurrent CMV infection was evaluated in 21 allogeneic T lymphocyte-depleted bone marrow transplantation (BMT) recipients who had been previously CMV seropositive. Of 17 patients with CMV infection, viruria was detected in 94%, CMV-specific IgA in 88% and IgM in 76%, and a fourfold rise in IgG in 65%. The median time between BMT and detection of viruria was 69 days, of IgA 70, of IgM 62, and of IgG 88 days. The IgM and IgA responses lasted for 14 and 30 days (median time), whereas high IgG titers persisted. Twelve patients developed CMV disease; in these the appearance of viruria, IgA, and IgM preceded the rise of IgG (P less than .02). CMV-specific IgA and IgM are valuable diagnostic tools in BMT recipients with recurrent CMV infection.

During 1985 in the Hadassah University Hospital we studied all hospitalized patients whose serum had been submitted for Legionella antibodies. Of 133 patients, 12 (9%) had legionellosis as diagnosed by serology, direct fluorescence, or culture. All Legionella cases appeared to be sporadic, nonseasonal, community-acquired pneumonia. There were no specific environmental co-factors or clustering. A significant predilection of the disease for immunosuppressed individuals was observed; the in-hospital mortality was high (5/12), especially if erythromycin therapy was delayed. L. pneumophila and L. bozemanii were the dominant etiological species. In Jerusalem, Legionella is not infrequently the etiological agent in community-acquired pneumonia in immunosuppressed patients.

Intravenous drug abuse is a principal factor in the spread of AIDS. In contrast to many countries in the Western world, most of the heroin addicts in Israel do not inject. This study attempts to clarify the link between the pattern of drug abuse and seroprevalence for human immunodeficiency virus (HIV) among volunteers attending a detoxification clinic in Jerusalem. Three hundred heroin abusers were interviewed about their drug habits and sexual preference. In addition, all participants underwent HIV serological testing. The majority of them took heroin by smoking, with only 19% injecting the drug. None of the participants in the study were HIV seropositive. An association is seen between the pattern of illicit drug use in Israel and the low incidence of AIDS in this country.

The efficacy of bronchoscopy with bronchoalveolar lavage for diagnosing 32 episodes of diffuse pulmonary infiltrates was studied in 30 nonAIDS immunocompromised patients. Bronchoalveolar lavage had an overall diagnostic yield of 84% (27 of 32 episodes). Bronchoalveolar lavage was noncontributive in five episodes of pneumonitis: drug induced in one, nonspecific in three and pneumonitis of unestablished etiology in one. Overall, the procedure is safe and did not miss diagnoses for which conventional treatment was available. Our data support the use of bronchoscopy with bronchoalveolar lavage as the primary diagnostic procedure in immunocompromised patients with diffuse pulmonary infiltrates.

Five term neonates diagnosed with immune thrombocytopenia were treated with 1 g/kg/day intravenous gamma-globulin. Clinical and laboratory evidence of thrombocytopenia resolved completely in 4 of the 5 patients after a single dose. Only 1 patient received a second dose of the drug. This treatment protocol requires less gamma-globulin than other protocols to safely reduce length of hospitalization.

Of the first 395 attendees at the AIDS clinic in Jerusalem, 32% were homo/bisexuals, 4% i.v. drug abusers (IVDAs), 24% persons with minimal risk for AIDS and 38% were persons having no risk. Human immunodeficiency virus (HIV) antibody rates were 7% for homosexuals, 29% for IVDAs, 1% for persons with minimal risk and 0% for persons at no risk. Israeli homosexuals had a significantly greater risk for HIV infection (9 of 35) if they had sexual contact with non-Israelis as compared with homosexuals who had contact with local partners only (0/91, P less than 0.001). The mean number of attendees per month increased by 431% during the 4 months following the first prime-time television program on AIDS. The largest mean increases occurred among persons at no risk (1 to 27.2), those with minimal risk (2.5 to 16.5), and among women (1.25 to 20.0). This report indicates that HIV infection among Israeli homosexuals has not yet reached U.S. proportions. It also shows that the TV program raised anxiety concerning AIDS among the general public, and probably encouraged the public to use HIV testing as part of a general health screening program.

In order to clarify the indications for splenectomy in patients with homozygous beta thalassaemia we studied, retrospectively, the basal pre-transfusion haemoglobin levels and blood transfusion requirements before and after splenectomy, in a series of patients with this disorder. Thirty-six patients, of whom 20 underwent splenectomy, were included in this study. Three groups of patients with homozygous beta thalassaemia were identified on the basis of clinical and laboratory findings. Two of the three groups consisted of 24 patients with beta thalassaemia major, subdivided retrospectively according to their response to splenectomy. The third group consisted of six patients with beta thalassaemia intermedia who had a comparably mild clinical course. In the first group of 16 patients with beta thalassemia major, monthly transfusions were required from the age of 6 months to 24 months and splenectomy resulted in temporary improvement for a period of 1-2 years. Thereafter, the transfusion requirements returned to pre-operative levels with no sustained improvements in base-line pretransfusion haemoglobin levels. Despite the fact that haematological improvement was temporary, it is felt that splenectomy is indicated in this group since the development and the general well-being of the children was significantly improved. In the second group of eight patients with beta thalassaemia major, transfusion requirements were relatively infrequent before 1-2 years, but after several years the transfusion requirement increased simultaneously with the development of 'hypersplenism'.

A rare case of acute promyelcytic leukemia (APL) is reported in a 7-year-old boy. The patient displayed the typical features of APL including impaction of the marrow with promyelocytes, marked elevation of the serum vitamin B12 and transcobalamin I levels and a hemorrhagic diathesis. The bleeding diathesis in the case was due to thrombocytopenia, and there was no evidence for disseminated intravascular coagulation.

The incidence of interstitial pneumonitis (IP) was reviewed in 80 consecutive patients who received allogeneic T lymphocyte-depleted bone marrow transplantation (BMT) for malignant and non-malignant diseases. Pretransplant conditioning used in malignant disorders included total lymphoid irradiation (TLI) 150 cGy x 4, total body irradiation (TBI) 200 cGy x 6, and cyclophosphamide (CY) 120 mg/kg. In non-malignant diseases conditioning included no TBI, but adjusted doses of TLI in addition to CY (severe aplastic anemia) or CY and busulfan (severe beta-thalassemia major). In the malignant group only one patient developed graft-versus-host disease (GVHD) grade I; IP developed in 12 out of 61 patients (19.7%) and IP-associated fatality occurred in five patients (8.2%). Cytomegalovirus (CMV) was associated with only two of the five fatal IP. In the non-malignant group there was no GVHD; one patient out of 19 (5.2%) had IP, which was fatal and not associated with CMV. These data indicate that fatal IP may appear in the absence of GVHD. The relatively low incidence of IP-related mortality in recipients of allogeneic T lymphocyte-depleted BMT suggests that although prevention of GVHD and elimination of drugs used for GVHD prevention may reduce the incidence of fatal pulmonary complications, other approaches have to be investigated for complete prevention of IP which still represents a major complication in patients with malignant hematologic disorders treated by allogeneic BMT.

Development of preimplantation mouse embryos, with or without the zona pellucida, in the presence of interferon (IFN) and mouse encephalomyocarditis (EMC) virus was studied using the in vitro culture method. The embryos (2- to 8-cell stages) were obtained from superovulated mice and cultured in modified Witten's medium under paraffin oil in 5% CO2 in air at 37 degrees C. Removal of the zona pellucida does not affect the subsequent development of the embryos: 90% of embryos with and 87% of embryos without the zona pellucida reached the morula-early blastocyst stages. Mouse IFN (10(4) units/ml) had no inhibitory effect on the developmental ability of the preimplantation embryos with or without the zona pellucida: 88 and 89% of the embryos in each group, respectively, reached the morula-early blastocyst stages. The preimplantation mouse embryos were sensitive to the embryotoxic effect of EMC virus: at a multiplicity of 20 infection particles per embryo the development of 43% of embryos was inhibited. The zona pellucida had no significant protective effect: Its removal changed only slightly the susceptibility of the preimplantation embryos to this virus. Pretreatment of embryos with IFN did not protect them from the embryotoxic effect of EMC virus. This work indicates that preimplantation mouse embryos appear to be resistant for both the antiviral and antiproliferative activities of IFN.

The unusual occurrence of both beta o-thalassemia and autoimmune hemolytic anemia (AIHA) in a 28-month-old child is reported to illustrate special diagnostic and therapeutic studies. The diagnosis of beta o-thalassemia was established by clinical, family and globin synthesis studies. The diagnosis of AIHA was confirmed by the shortened survival of transfused autologous and homologous red blood cells and by positive direct antiglobulin tests. During treatment of the AIHA were corticosteroids and various immunosuppressive drugs, globin synthesis studies were performed to evaluate the coincidental effects on gamma/alpha-globin chain synthetic ratios. A 50% increase in the gamma/alpha synthetic ratio during cyclophosphamide treatment suggests that further studies of the possible benefits of cytotoxic drug therapy in beta-thalassemia may be indicated.

The present report summarizes our experience in applying a new approach in bone marrow transplantation for the treatment of beta-thalassemia major. Ex-vivo pretransplant T-lymphocyte depletion with CAMPATH-1 was used for prevention of acute and chronic graft versus host disease and total lymphoid irradiation was added for the conditioning regimen for abrogation of potential rejection of T-cell depleted marrow allografts. Ten patients with homozygous beta-thalassemia major were 9-48 months of age (median 18.5 months) and received HLA-identical allogeneic T-cell depleted marrow after treatment with total lymphoid irradiation, busulfan and cyclophosphamide. Seven patients are alive and free of disease, 3-46 months post-transplantation. The actuarial probability of survival and of disease-free survival at two years was 70%. Three patients died: one of intracranial hemorrhage post-transplantation, one from busulfan interstitial pneumonitis, and one who rejected the first graft and developed fatal chronic graft versus host disease after a second transplant. Seven patients are alive and well with follow-up of 3-45 months, with no signs of acute or chronic GVHD. We conclude that T-cell depleted bone marrow transplantation is indicated for homozygous transfusion dependent young patients with beta-thalassemia who are minimally transfused, particularly in areas where optimal conventional therapy is not feasible.

Noma is a very rare gangrenous infection of the oral cavity usually associated with debilitating diseases, immunosuppression, or malnutrition. Its development in a previously healthy 13-year-old boy with perforated appendicitis is presented. Streptococcus bovis type II and E coli were isolated from the noma and Streptococcus bovis, Bacteroides fragilis, and Bacteroides asacharolyticus from the peritoneal fluid. A transient impaired immune cellular function was found and may have contributed to the development of the noma in this child.

Four cases of bilateral congenital choanal atresia are presented. Three of them (75 per cent) were shown by Electric Response Audiometry (ERA) tests to have, in addition, congenital nerve deafness; and two had other congenital anomalies. Thus, congenital nerve deafness should be considered as a possible congenital anomaly associated with choanal atresia. Early diagnosis and treatment of congenital choanal atresia can prevent death from asphyxia during the neonatal period, but after surgical correction of the atresia the possible existence of additional anomalies has to be determined and treated. By the use of electric response audiometry we are able to detect sensorineural hearing loss during the neonatal period and can plan the rehabilitation of deaf infants.

A five-year-old boy of Iranian origin with multiple anomalies is described. His parents are first and second cousins. He presented with short stature, psychomotor retardation, microcephaly, ptosis, dacryostenosis, partial left nerve deafness, high arched palate, bifid uvula, total fusion between incisors, asymmetric preaxial and postaxial polysyndactyly, brachyphalangy, kyphosis and spina bifida occulta of S1. To our knowledge, a similar case has not been reported previously.

Pneumoscrotum developed after percutaneous liver biopsy in a 5-yr-old boy. Fifteen minutes after the procedure an enlargement of the right scrotum was noted. X-rays revealed a very small right-sided pneumothorax, subcutaneous air dissecting along the right chest and right abdominal walls and a confluent pocket of air in the right scrotum. We suggest that the air from the pleural cavity penetrated the superficial fascia in the upper right abdomen and dissected beneath the deep membranous layer into the scrotum.

Six immunodeficient boys were found to have agammaglobulinemia and lack circulating B cells. These patients could be divided into two groups based on bone marrow findings and clinical course. In one group, pre-B cells and lymphocytes were present at normal frequencies and in normal absolute numbers. Recurrent serious infections were documented in the first few months of life in these patients, and this consequently led to early diagnosis. In the second group, pre-B cells were virtually undetectable. Patients in this group did not present with recurrent infections until the second year and were thus diagnosed later than were those in the first group. Childhood agammaglobulinemia with deficiency of both pre-B and B lymphocytes appears to be a different disease from X-linked infantile agammaglobulinemia. This disease may involve an arrest of B-lineage cell development at an earlier stage than that responsible for X-linked agammaglobulinemia.

The single-dose pharmacokinetics of two dosages of imipenem-cilastatin (1:1), 10 and 25 mg/kg, were studied in ten children. Plasma concentrations, half-lives, and areas under the curve of both imipenem and cilastatin was significantly greater at the 25 mg/kg dosage but the half-lives and clearances of the two drugs were similar to each other only at the larger dose. After a 25 mg/kg dose, the mean peak and trough (6 hr) plasma concentrations of imipenem were 78.8 and 0.68 micrograms/ml, respectively, and the half-lives of imipenem and cilastatin were 1.12 and 0.97 hr, respectively. Urinary excretion of imipenem was 43-47% during the 6 hr following administration of either dosage. No clinical or laboratory toxicity was noted. A 25 mg/kg dose of imipenem-cilastatin maintains serum concentrations of imipenem above the minimum inhibitory concentration (MIC) of potential pathogens for 4-6 hr and seems appropriate for multiple-dose studies. Our data suggest that a minimum dosage, greater than 10 mg/kg, of cilastatin may be required to prolong the half-life of imipenem to adult values.

An immunocompromised patient, 6 weeks after bone marrow transplantation, developed extensive skin infection due to Trichophyton rubrum. Because she could not tolerate ketoconazole and was hypersensitive to griseofulvin, she received itraconazole with complete recovery within 30 days. This case demonstrates that itraconazole may be effective treatment for dermatophytosis, even in immunocompromised hosts, and that there is no cross-reactivity between ketoconazole and itraconazole.

The occurrence of HSV infection and the effect of prophylaxis with oral acyclovir were evaluated prospectively in 34 consecutive patients undergoing bone marrow transplantation (BMT). All allogeneic BMT procedures involved T-lymphocyte depletion for prevention of graft-vs.-host disease (GVHD). Five HSV-seronegative patients did not receive acyclovir, and they did not develop HSV infection. Oral acyclovir was administered to 15 HSV-seropositive BMT recipients; 14 untreated HSV-seropositive BMT recipients served as a control group. The adult dose of acyclovir was 400 mg three times a day on Days -6 to +14 and 200 mg three times a day on Days +15 to +90. Children received 500 mg/m2 per day divided into three equal doses on Days -6 to +14 and 250 mg/m2 per day again divided into three on Days +15 to +90. In the group on prophylaxis, only one developed HSV infection during the time prior to engraftment. In the reference group, 12 of 14 (85.7%) developed oral HSV infection within 0 to 16 days (median 11 days) after the transplantation. Time for engraftment (duration of neutropenia) was shorter in patients receiving acyclovir. After engraftment, HSV infection was not observed during administration or following discontinuation of acyclovir on Day 90, but occurred in three patients in whom acyclovir was discontinued on Days 25, 35 and 40 after BMT. In the untreated group, two patients had recurrence of HSV infection on Days 40 to 60, and one had two infectious episodes. GVHD occurred in only two recipients, neither of whom had HSV infection. We conclude that the incidence of HSV infection during the period until engraftment in recipients of T-lymphocyte-depleted BMT is high, similar to that reported by others in recipients of whole BMT. Relatively low-dose oral acyclovir administered for 90 days can effectively prevent HSV infections in previously HSV-seropositive BMT recipients and may also shorten the period until engraftment.

Two patients undergoing bone marrow transplantation developed severe gastrointestinal symptoms, one during the peri-transplantation period and the other several months post-transplantation and following documented intestinal graft-versus-host disease. After detection of Giardia lamblia trophozoites in a stool specimen from one patient and a duodenal aspirate from the other, treatment with metronidazole was administered and all symptoms resolved. Giardiasis should be considered in transplant patients with diarrhea. Negative stool examinations do not rule out this possibility, and consideration should be given to examining a sample of small intestinal contents for Giardia trophozoites.