Evidence that intrathymic islet transplantation does not prevent diabetes or subsequent islet graft destruction in RT6-depleted, diabetes-resistant BioBreeding/Worcester rats.

Pancreatic islet allografts transplanted intrathymically are accepted and restore normoglycemia in streptozotocin-diabetic rats given one injection of antilymphocyte serum. Intrathymic allografts similarly restore normoglycemia in diabetes-prone (DP) Bio-Breeding (BB) rats that have developed spontaneous autoimmune diabetes. Intrathymic islets also reduce the frequency of subsequent diabetes when transplanted prophylactically into young DP rats. These findings suggest that intrathymic transplantation can prevent not only allograft rejection, but also the appearance and recurrence of autoimmune tissue destruction. To explore these hypotheses further, we attempted both to confirm previous studies and to extend them to another model of autoimmune diabetes, the RT6-depleted diabetes-resistant (DR) BB rat. Fewer than 1% of DR-BB rats develop spontaneous diabetes, but most become hyperglycemic after in vivo immune elimination of RT6+ T cells. Using the protocols described in the literature, we observed the following: (1) Consistent with previous reports, intrathymic islet allografts survived indefinitely in streptozotocin-diabetic, antilymphocyte serum-treated, non-BB recipient rats. (2) Consistent with previous reports, intrathymic islet grafts produced long-term normoglycemia in diabetic DP-BB rats and also reduced the frequency of spontaneous diabetes in young animals transplanted prophylactically. (3) In contrast, intrathymic islets (iso- and allografts) neither prevented nor reversed diabetes in RT6-depleted DR rats. We hypothesize that intrathymic islet grafts survive in DP-BB rats because they are lymphopenic and immunocompromised, whereas immunocompetent diabetic DR rats successfully recapitulate the autoimmune disease process. Although intrathymic allograft transplantation is postulated to induce a state of tissue-specific tolerance, our results indicate that this tolerant state may not extend to autoimmune destruction of either isografts or allografts.

Preferential elevation of protein kinase C isoform beta II and diacylglycerol levels in the aorta and heart of diabetic rats: differential reversibility to glycemic control by islet cell transplantation.

In the present study, we have measured protein kinase C (PKC) specific activities and total diacylglycerol (DAG) level in the aorta and heart of rats, which showed that after 2 weeks of streptozotocin (STZ)-induced diabetes, membranous PKC specific activity and total DAG content were increased significantly by 88% and 40% in the aorta and by 21% and 72% in the heart, respectively. Hyperglycemia was identified as being a causal factor since elevated glucose levels increased DAG levels in cultured aortic endothelial and smooth muscle cells. Analysis by immunoblotting revealed that only alpha and beta II PKC isoenzymes are detected in these two tissues and vascular cells among those studied. In STZ-induced diabetic rats, beta II isoenzyme is preferentially increased in both aorta and heart, whereas PKC alpha did not change significantly. The increases in membranous PKC specific activity and DAG level are observed in both spontaneous diabetes-prone diabetic BB rats as well as in STZ-induced diabetic BB and Sprague-Dawley rats, which persisted for up to 5 weeks. After 2 weeks of diabetes without treatment, the normalization of blood glucose levels for up to 3 weeks with islet cell transplants in STZ-induced diabetic BB rats reversed the biochemical changes only in the heart, but not in the aorta. These results suggest that PKC activity and DAG level may be persistently activated in the macrovascular tissues from diabetic animals and indicate a possible role for these biochemical parameters in the development of diabetic chronic vascular complications.

Pneumocystis carinii infection of the thyroid in a hypothyroid patient with AIDS: diagnosis by fine needle aspiration biopsy.

A 49-yr-old homosexual man with acquired immunodeficiency syndrome presented with a left-sided neck mass. He was found to have a firm goiter. He was clinically euthyroid, but had laboratory evidence of primary hypothyroidism. Radioactive iodine scan of the thyroid showed homogeneous uptake over an enlarged right lobe and absence of uptake over the left lobe. Two fine needle aspiration biopsies of the thyroid revealed the presence of Pneumocystis carinii (P. carinii) organisms on the Gomori's methenamine silver strain. After courses of iv and oral therapy with trimethoprim-sulfamethoxazole, a third fine needle aspiration biopsy failed to reveal any organisms. A repeated radioactive iodine scan of the thyroid showed return of uptake over the left lobe. Thyroid function tests normalized with levothyroxine, and the goiter decreased in size. To our knowledge, this is the first report of hypothyroidism associated with P. carinii infection of the thyroid. P. carinii infection should be considered in the differential diagnosis of human immunodeficiency virus infected individuals presenting with cold thyroid nodules. Fine needle aspiration biopsy is a valuable tool in assessing these patients.

Helicobacter pylori infection in patients with acquired immune deficiency syndrome.

A controlled study was conducted on patients with human immunodeficiency virus (HIV) infection referred for upper endoscopy to evaluate the prevalence of Helicobacter pylori (H. pylori) infection. Four different stains and culture for H. pylori were performed on biopsy specimens from the gastric antrum. Sixteen (40%) of 40 patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) were diagnosed to be infected with H. pylori versus 14 (39%) of 36 age-matched control patients. Eight of 15 AIDS/ARC patients without AIDS-related esophagogastroduodenal findings (53%) were infected with H. pylori versus 8/25 (32%) with endoscopic findings typical of AIDS. No invasion of the lamina propria by H. pylori was noted in any patient. Active chronic gastritis was present in 60% of AIDS/ARC patients and 61% of controls. Fifty-eight and 59%, respectively, of active chronic gastritis cases were infected with H. pylori. All the H. pylori infections, except one, were found in patients with chronic gastritis. In AIDS/ARC patients, H. pylori infection and active chronic gastritis are as common as in other patients referred for upper endoscopy. They may play a pathogenic role, especially when endoscopic AIDS-related findings are lacking. Cell-mediated immune deficiency does not appear to increase the risk of infection with H. pylori.

Drug resistant tuberculosis among the homeless in New York City.

The purpose of this study was to compare the frequency of infections due to drug resistant Mycobacterium tuberculosis between homeless and nonhomeless populations in an urban community hospital. We retrospectively examined the mycobacteriology registry of this hospital for culture-proven, susceptibility-tested cases of M tuberculosis disease from 1982 to 1987. Clinical records were analyzed for age, ethnicity, sex, residence, and history of alcoholism, intravenous drug abuse, acquired immunodeficiency syndrome, or previous tuberculosis. Of a total of 132 cases, 53 patients were homeless and 79 were not. Drug resistance was found in 21% of the isolates from homeless individuals and 8% of those from nonhomeless persons. Resistance to isoniazid was found in 19% and 1% (p less than 0.01), and for two or more drugs in 15% and 0% (p, 0.01), respectively. Forty-two patients were black, and among them, resistance to one or more drugs was 26.2%, versus 6.6% in nonblacks (p less than 0.01). Ten of 24 homeless blacks had resistant organisms, as opposed to 1 of 18 nonhomeless blacks (p less than 0.05). No other significant differences were noted for the other variables. To our knowledge, this is the first comparison of drug-resistant tuberculosis between homeless and nonhomeless patients using an internal control group. Forty percent of isolates from homeless blacks were resistant, two thirds to both isonlazid and rifampin. These findings support the use of an initial four-drug regimen to treat tuberculosis in this specific population.

High Staphylococcus aureus nasal carriage rate in patients with acquired immunodeficiency syndrome or AIDS-related complex.

Staphylococcus aureus has been reported to cause a high number of infections and septicemias, often related to intravenous catheters, in patients with acquired immunodeficiency syndrome (AIDS). Our objective was to assess the frequency of S. aureus nasal carriage among patients with AIDS or AIDS-related complex (ARC). The nasal carriage rate of S. aureus was determined within 24 hours of admission in 64 consecutively hospitalized patients with AIDS or ARC. Intravenous drug abusers were excluded. A control group of 64 patients with other diseases was also tested. Of 64 patients with AIDS or ARC, 35 (55%) were nasal carriers of S. aureus, compared with 18 (28%) of 64 control patients. Recent hospitalization did not influence carriage rate, nor did the recent use of antibiotics or zidovudine. The significant S. aureus carriage rate in patients with AIDS or ARC may contribute to the high incidence of intravenous catheter-related S. aureus infections in this population.

Clinical features and management of severe dermatological reactions to drugs.

Cutaneous adverse drug reactions are a frequent occurrence and have been reported in more than 2% of hospitalised patients. Among the most commonly involved drugs are sulphonamides, penicillins, anticonvulsants and non-steroidal anti-inflammatory drugs. Two groups of mechanisms are involved in the pathogenesis of drug reactions: immunological, with all 4 types of hypersensitivity reactions described; and non-immunological, accounting for at least 75% of all drug reactions. Besides minor skin reactions like urticaria, maculopapular rash, fixed eruptions or erythema nodosum, which are generally self-limited, severe life-threatening manifestations also occur. Erythema multiforme is secondary to drugs in half the cases; the minor form is characterised by typical target and iris lesions and is usually benign. However, a much more severe condition, erythema multiforme major or Stevens-Johnson syndrome, is associated with mucosal, ocular and visceral involvement, and carries a mortality of 5 to 15% if untreated. Toxic epidermal necrolysis, which could represent an even more dramatic form of the same disease, is characterised by severe widespread erythema, blisters and loss of skin in sheets, with denudation of more than 10% of the body surface area. This entity is frequently due to drugs. Mortality is 25 to 70%, and 90% of the survivors will have sequelae. Exfoliative dermatitis is an erythematous scaling disease often produced by drugs and carrying significant mortality. Photodermatitis may at times present with severe eczematous features. For clinical and epidemiological reasons it is important to try to identify the culprit drug following an approach based on previous experience with the drug, timing of events, patient reaction to dechallenge, patient reaction to rechallenge (if feasible), alternative aetiological candidates, and drug concentration or evidence of overdose. Management of severe skin reactions to drugs should require admission to a burn unit, where patients should be placed in warmed air-fluidised beds, receive excellent nursing care, analgesics and tranquillisers. Peeling necrotic epidermis should be removed and denuded dermis covered with biological grafts or synthetic dressings. Fluid balance must be adequately maintained; nutritional support and careful monitoring of early signs of skin infections is mandatory to ensure immediate antimicrobial treatment. Ocular care must be excellent to avoid serious sight-threatening sequelae. Steroids are presently not recommended. With these therapeutic modalities, morbidity and mortality can be markedly decreased.

Infections associated with Hickman catheters in patients with acquired immunodeficiency syndrome.

PURPOSE: Hickman catheters are frequently used as convenient long-term venous access in patients with acquired immunodeficiency syndrome (AIDS). These patients seem to be at increased risk for bacterial infections of intravenous devices. The aim of our study was to determine the frequency of Hickman catheter infection in patients with AIDS as compared with that in other patients. PATIENTS AND METHODS: We analyzed the records of 69 patients who underwent 71 consecutive Hickman catheter placements during a one-year study period. RESULTS: Forty-six Hickman catheters were inserted in 44 patients with AIDS, and 25 Hickman catheters were placed in 25 other patients. There were 18 infections: 16 occurred in patients with AIDS, and two developed in the control group (p less than 0.05). The 16 infections in AIDS were as follows: five exit site, five septicemias, two tunnel, one septic phlebitis, and three probable Hickman catheter-related. Staphylococcus aureus was responsible for 14 cases (87%); Staphylococcus epidermidis was responsible for four cases (25%). Mean onset of infection was 32 days, but seven patients were diagnosed in the first eight days after Hickman catheter insertion. Fever occurred in all patients with early infection, leukopenia was present only in three; infusion of parenteral nutrition did not increase the risk. Two early infections were fatal. The rate of Hickman catheter infection in patients with AIDS was 0.47 per 100 catheter days, as compared with 0.09 in the control group. CONCLUSION: Our findings underscore the need for using Hickman catheters only when absolutely indicated in patients with AIDS, since the risk of serious infectious complications appears to be high.

Cardiopulmonary resuscitation in patients with the acquired immunodeficiency syndrome. A prospective study.

To study the outcome of cardiopulmonary resuscitation (CPR) in patients with acquired immunodeficiency syndrome (AIDS), data on CPR in hospitalized patients were collected prospectively during a one-year study period. Of 43 consecutive patients with AIDS who underwent CPR, 23% were revived in the initial attempt, whereas of 293 patients with other diseases 42% were revived. One (2.3%) of 43 patients with AIDS survived until hospital discharge, and his arrest was iatrogenic, as opposed to 19 (6.5%) of 293 patients with diseases other than AIDS. A respiratory mechanism for the arrest was significantly more common in patients with AIDS. The duration of the unsuccessful attempt did not vary significantly; a higher number of temporary pacemakers was used in patients with diseases other than AIDS indicating a more invasive approach. Survival until hospital discharge is minimal in our series of patients with AIDS, undergoing CPR. We recommend that informative discussions take place early in the course of the disease to provide patients with a better understanding of the available options in case of cardiorespiratory arrest.