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Biomedical subjects

B C Herzlich

Publications and source records attributed to B C Herzlich.

15 recordsLinked to original sources

Bronchiolitis obliterans organizing pneumonia as the first manifestation of polymyositis.

Bronchiolitis obliterans organizing pneumonia (BOOP) preceding polymyositis is rare. In this report, a 51-year-old patient with fever, nonproductive cough, and dyspnea had bilateral basal interstitial infiltrates on chest roentgenogram. Open lung biopsy was consistent with BOOP. Prednisone therapy led to improvement, but 8 weeks later, fever, cough, and weakness of the arms and legs developed because the patient had not been compliant with the prednisone regimen. The creatine kinase (CK), the macrophage inflammatory protein (MIP-1), and the tumor necrosis factor (TNF-alpha) were elevated. Anti-Jo-1 antibody was not present. Quadriceps femoris muscle biopsy was compatible with polymyositis. After a second course of corticosteroid therapy, the patient became afebrile, the dyspnea resolved, the pulmonary infiltrates decreased, and the muscle strength improved. The serum CK, MIP-1, and TNF-alpha levels declined significantly. This is only the second reported case of BOOP preceding polymyositis. Patients with idiopathic BOOP should have follow-up for the possible development of connective tissue disorders including polymyositis.

Anti-Inflammatory Agents↗

Impaired antibody responses to pneumococcal polysaccharide in elderly patients with low serum vitamin B12 levels.

OBJECTIVE: To determine whether immunocompetent elderly patients with low serum vitamin B12 levels have impaired serum antibody responses to the 23-polyvalent pneumococcal polysaccharide vaccine. DESIGN: Controlled, prospective cohort study. MEASUREMENTS: 15 patients with low serum vitamin B12 levels and 15 age- and diagnosis-matched patients with normal levels were vaccinated. Serum antibody titers to 12 pneumococcal serotypes were measured by radioimmunoassay before and 4 weeks after vaccination. RESULTS: The difference between the geometric mean of the vaccine antibody titers before and after vaccination for all 12 serotypes was lower (P = 0.005) in the patients with low vitamin B12 levels than in the patients with normal levels. When mean corpuscular volume and age were controlled for, vitamin B12 remained an independent predictor of antibody response (P = 0.005). Erythrocyte mean corpuscular volume was also an independent predictor of the increase in titer (P = 0.03). CONCLUSIONS: Patients with low vitamin B12 levels had impaired antibody responses to pneumococcal vaccine. Further study is necessary to determine whether treatment with vitamin B12 can enhance specific immunoglobulin synthesis and improve the clinical efficacy of the pneumococcal vaccine in patients with low vitamin B12 levels.

Aged↗

Relationship among homocyst(e)ine, vitamin B-12 and cardiac disease in the elderly: association between vitamin B-12 deficiency and decreased left ventricular ejection fraction.

We evaluated the association of moderate hyperhomocyst(e)inemia and vitamin B-12 status with coronary artery disease (CAD) and left ventricular ejection fraction in 367 elderly patients undergoing coronary angiography. The extent of CAD was scored, left ventricular ejection fraction was assessed and vitamins B-12 and folate and the metabolites homocyst(e)ine, methylmalonic acid and 2-methylcitric acid were measured. There was no significant trend in change in homocyst(e)ine as the extent of CAD increased. There was an association between vitamin B-12 deficiency, i.e., vitamin B-12 < 221 pmol/l and homocyst(e)ine > 16 nmol/ml and low left ventricular ejection fraction (P = 0.014). Of 105 samples, selected for vitamin B-12 < 221 pmol/l or high normal vitamin B-12 and folate levels, metabolites including methylmalonic acid revealed a specific diagnosis of vitamin B-12 deficiency in 18 patients. The trend among these vitamin B-12-deficient patients and low left ventricular ejection fraction was significant (P = 0.028). In vitro studies on rat heart revealed that nitrous oxide in the presence of 200 microM/l methionine reduced contractility of the heart. In conclusion, vitamin B-12-deficient patients had significantly lower left ventricular ejection fractions than nonvitamin B-12-deficient patients. Whether low left ventricular ejection fraction results in malabsorption of vitamin B-12 and vitamin B-12 deficiency, or conversely, whether vitamin B-12 and its marker, elevated homocyst(e)ine, depress left ventricular function warrants further evaluation.

Aged↗

Rhabdomyolysis and myoglobinuric acute renal failure associated with classic heat stroke.

Classic heat stroke is a disorder of thermal regulation that predominantly affects elderly patients during heat waves. In contrast to exertional heat stroke, rhabdomyolysis and myoglobinuric acute renal failure are considered to be unusual manifestations of classic heat stroke. We retrospectively reviewed the charts of seven patients admitted to Maimonides Medical Center with classic heat stroke over a 3-day period during a heat wave in July 1993. Three of these patients with classic heat stroke had rhabdomyolysis, but no renal failure; two completely recovered; and one had an ataxic gait disturbance. Three additional patients had rhabdomyolysis and myoglobinuric acute renal failure; one of them completely recovered, one survived with quadriplegia, and one died. Our findings suggest that rhabdomyolysis and myoglobinuric acute renal failure are common manifestations of classic heat stroke. Recognition of this complication warrants rigorous hydration and alkalinization of the urine to prevent or attenuate myoglobinuric acute renal failure.

Acute Kidney Injury↗

Hepatic artery aneurysm associated with acute gastroenteritis: successful treatment after intraperitoneal rupture.

A 62-year-old multiparous woman was hospitalized because of nausea, vomiting, anorexia, loose stools, and abdominal discomfort for 3 days. During the hospitalization, she suddenly had hemorrhagic shock with electromechanical dissociation. Intraoperatively, she was found to have a ruptured hepatic artery aneurysm, which was successfully ligated. The patient fully recovered. We believe hepatic artery aneurysms should be considered in the differential diagnosis of patients with nonspecific gastrointestinal symptoms if unexplained anemia, jaundice, and especially hypotension occur.

Acute Disease↗

Reversal of apparent AIDS dementia complex following treatment with vitamin B12.

The human immunodeficiency virus (HIV)-associated dementia complex is characterized by difficulties in concentration and memory followed by apathy, social withdrawal and motor dysfunction. Decreased serum vitamin B12 levels occur in up to 20% of patients with acquired immune deficiency syndrome (AIDS) and may adversely contribute to the haematologic and neurologic dysfunction which is frequently attributed to the human immunodeficiency virus. We describe a patient with AIDS who presented with an apparent advanced AIDS dementia complex. There was an associated low serum vitamin B12 resulting from malabsorption due to low gastric intrinsic factor secretion. Following treatment with vitamin B12 the symptoms resolved over a 2-month period. We believe that the AIDS dementia complex represented a reversible adverse synergistic interaction between the human immunodeficiency virus and vitamin B12 deficiency.

AIDS Dementia Complex↗

Presence of cross-reactive antibodies to HTLV-1 and absence of antigens in patients with multiple sclerosis.

Antibodies to HTLV-1, as determined by ELISA, were highly elevated in the serum samples of four out of four (100%) patients with TSP, moderately elevated in four out of four (100%) HTLV-1 carriers, slightly elevated in 12 out of 34 (35%) patients with MS, and absent from the serum samples of 34 normal subjects. Western blot analysis showed that the antibodies to HTLV-1 antigens in MS serum were heterogeneous. Cultivation of peripheral blood lymphocytes (PBLs) from patients with MS or normal subjects did not generate HTLV-1 core p19 antigen in the supernatant of culture medium, whereas cultivation of PBLs from patients with TSP and carriers of HTLV-1 generated core p19 antigen after 3 days for up to 28 days of cultivation. HTLV-1 antigens were also expressed on the surface of PBLs in three out of four patients with TSP and in two out of four HTLV-1 carriers on days 14 and 28 of cultivation, as measured by indirect immunofluorescence or alkaline phosphatase staining, but were not found in PBLs of any of 34 patients with MS or 34 normal subjects. The data indicate that although cross-reacting antibodies appear in the serum of some patients with MS, not enough evidence exists to suggest that HTLV-1 antigen is being produced in MS or that HTLV-1 plays a role in the pathogenesis of this disease.

Adult↗

Needlestick injury: blood, mononuclear cells, and acquired immunodeficiency syndrome.

INTRODUCTION: Because transmission of HIV to health care workers after needlestick injury has occurred mainly a result of deep insertion of large gauge needles, blood and viable mononuclear cells transferred after needlestick injury were measured. METHODS: Needles of 20 to 27 gauge were filled with HIV-1 seropositive blood and inserted through extracorporeal human skin or parafilm covering physiologic saline solution modified Drabkin's solution, or culture medium, or inserted directly into one of these fluids, to a depth of one third of the needle length (0.5 inch) for 1 second. Volume of blood transferred was measured by both modified Drabkin's method and by chromium 51 labeling of red blood cells. Transfer of viable mononuclear cells was measured by growth in culture medium containing autologous feeder cells. RESULTS: The volume of blood transferred from a needle passed through skin varied from 312 +/- 69 nl from a 20-gauge needle to 14 +/- 4 nl from a 27-gauge needle, as measured by modified Drabkin's technique, and from 404 +/- 80 nl to 12 +/- 3.1 nl, as measured by chromium 51 labeling of red blood cells. The volume of blood transferred from a needle passed through parafilm was twice that transferred through skin. The volume of blood transferred through skin was 40% that transferred directly into fluid not covered by any barrier; blood transferred through parafilm was 80% of that transferred directly. When needles containing blood were inserted into culture medium for 1 second in the absence of a barrier, at least one viable mononuclear cell was almost always transferred to fluid from all gauges of needle tested. Insertion of needles through skin prevented transfer of all viable mononuclear cells from only 3% to 5% of 20- to 23-gauge needles, and from 12% to 32% of 26- and 27-gauge needles. Parafilm was an even less effective barrier than skin. Insertion of needles through parafilm completely prevented transfer of viable mononuclear cells from no 20- to 23-gauge needles and from only 5% to 10% of 26- and 27-gauge needles. CONCLUSION: The volume of blood transferred after needle insertion through skin for 1 second varied with the gauge of the needle and was 30-fold higher from a 20-gauge than from a 27-gauge needle. Variable mononuclear cells were transmitted after insertion through skin from more than 95% of 20- to 23-gauge needles and from 68% to 88% of 26- and 27-gauge needles. Parafilm was less effective than skin in reducing transmission of blood and viable mononuclear cells.

Acquired Immunodeficiency Syndrome↗

Decreased intrinsic factor secretion in AIDS: relation to parietal cell acid secretory capacity and vitamin B12 malabsorption.

AIDS-associated gastric secretory failure has been characterized by decreased secretion of acid, pepsin, and gastric juice volume. To determine whether decreased intrinsic factor secretion and vitamin B12 malabsorption occur in this entity, we performed prospective measurements of maximal acid output, intrinsic factor output, vitamin B12 absorption, serum vitamin B12, and holotranscobalamin II in 10 consecutive AIDS patients. Four of 10 patients had low maximal acid output, i.e., < or = 1.5 mEq/h (control = 12.8 +/- 9.0, range 2.5-25 mEq/h). Four patients had low intrinsic factor output, i.e., < or = 1.1 microgram/h (control = 8.2 +/- 6.9, range 3.1-19.4 micrograms/h). One patient with low intrinsic factor output had low serum vitamin B12 and a Schilling test consistent with pernicious anemia. A second patient with very low intrinsic factor output (0.16 micrograms/h) had low parts I and II Schilling tests; malabsorption most likely resulted from both low intrinsic factor secretion and ileal disease. One of three vitamin B12 malabsorbing patients, with normal serum vitamin B12, had low holotranscobalamin II, 25 pg/ml (control holotranscobalamin II = 76 +/- 44, range 44-152 pg/ml). Maximal acid output and intrinsic factor output did not correlate in AIDS (r = 0.36, p = 0.30) in contrast to the expected correlation in controls (r = 0.91, p = 0.03). We conclude that low intrinsic factor secretion is common in AIDS and contributes to vitamin B12 malabsorption. Decreased parietal cell secretion of intrinsic factor and acid may occur independently in human immunodeficiency virus-associated gastric secretory failure. Low holotranscobalamin II, an early manifestation of vitamin B12 malabsorption, results in decreased delivery to vitamin B12-dependent tissues prior to depletion of serum vitamin B12. Regular supplementation with vitamin B12 may therefore be warranted in patients with advanced HIV infection.

Acquired Immunodeficiency Syndrome↗

Synergy of inhibition of DNA synthesis in human bone marrow by azidothymidine plus deficiency of folate and/or vitamin B12?

The effect of azidothymidine (Zidovudine, AZT) on pyrimidine (thymidine, deoxyuridine, and thymidine triphosphate) incorporation into DNA in folate- and/or vitamin B12-deficient and normal human bone marrow cells was studied to investigate whether such vitamin deficiency affects susceptibility to AZT-induced hematologic toxicity. Bone marrow cells from 12 patients were studied: 5 had folate and/or vitamin B12 deficiency; 7 controls included 5 with anemia related to chronic disease and 2 with iron deficiency. At 0.2 microM AZT (3 hr, 37 degrees C), the approximate pharmacologic serum trough level, pyrimidine incorporation into DNA was suppressed by 12 to 19% in folate- and/or vitamin B12-deficient cells and by 16 to 23% in normal cells. At 2.0 microM AZT (3 hr, 37 degrees C), the approximate pharmacologic serum peak level, this was suppressed by 15 to 40% in folate- and/or vitamin B12-deficient cells and by 32 to 47% in controls. Deoxyuridine incorporation into DNA was inhibited significantly greater than thymidine at 2.0 microM AZT (3 hr, 37 degrees C) in both groups. Inhibition of deoxyuridine incorporation was not reversed with methyltetrahydrofolate or vitamin B12. There tended to be less striking suppression by AZT of deoxyuridine incorporation into DNA in bone marrow cells from vitamin B12-deficient patients, which was made more striking by adding vitamin B12. This suggests that some of what passes for "AZT damage" to bone marrow cells may in fact be coincident deficiency of vitamin B12. AZT inhibition of DNA synthesis in 3 hr bone marrow cultures is relatively consistent in a variety of hematologic disorders. As approximately two-thirds of AIDS patients appear to be in negative balance with respect to folate and/or vitamin B12, the fact that AZT-induced inhibition of pyrimidine incorporation into DNA is occurring in cells which may be megaloblastic, i.e., in a state of impaired DNA synthesis, suggests that these cells may be more susceptible to AZT toxicity. The data also support the notion that AZT inhibition results predominantly from termination of DNA chain elongation. Whether folate or vitamin B12 supplementation may partially overcome apparent "AZT inhibition" of DNA synthesis (hematologic toxicity) and whether the benefit of such therapy exceeds the risk will require further study.

Bone Marrow↗

Detection of HIV antibody and antigen (p24) in residual blood on needles and glass.

There is a significant rate of percutaneous injury with needles during the care of patients with acquired immunodeficiency syndrome (AIDS). Following puncture injury, it is recommended that the source of the contaminating blood be checked, and if human immunodeficiency virus-type 1- (HIV-1)-seropositive, zidovudine prophylaxis be considered. As the source of contaminating blood may be unknown, we studied the detectability of HIV-1 antibody and circulating antigen (p24) in the residual blood from needles and pieces of glass at various intervals following exposure to blood. The residual volume of blood remaining in needles varied from 183 +/- 50 microliters for a 20 G needle to 7.8 +/- 1 microliter for a 27 G needle, and the residual blood on small pieces of glass varied from 23 microliters for a piece weighing 558 mg to 2 microliters for a piece weighing 21 mg. Analysis of washed samples of residual blood from all 20 G through 26 G needles and from broken pieces of glass larger than 0.41 g that had been exposed to HIV-1-seropositive blood and left at room temperature for one hour, one day and one week resulted in positive tests for HIV-1 antibody by enzyme-linked immunosorbent assay (ELISA), immunofluorescence and Western blot assays. The circulating antigen was detected in residual blood of 20 G through 26 G needles, but not from contaminated pieces of glass. This technique could be applied to situations where a healthcare worker pricked him- or herself with a needle or with a piece of glass that had been contaminated with blood of unknown seroreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Western↗

Cobalamin-specific R binder in pernicious anemia gastric juice: production by digestive enzyme action on saliva R binder.

We found in four of five pernicious anemia gastric juices a partly degraded R binder which was cobalamin specific and has an apparent molecular weight of 60-70,000 daltons. Twenty-nine to 74% (4.8-27.0 ng/ml) of the corrinoid binding capacity could not be blocked by cobinamide (a noncobalamin corrinoid). The fifth pernicious anemia gastric juice and five nonpernicious anemia gastric juices had minimal amounts of this binder (2.5 and 2.2 +/- 1.4 ng/ml). Scatchard analysis revealed that cobalamin-specific R binder has 1000-fold lower affinity for cobinamide than cobalamin. Increasing quantities of trypsin and/or chymotrypsin digested increasing amounts of saliva R binder and an increasing percentage of the remaining digest-resistant R binder acquired cobalamin specificity. Partly degraded R binder in pernicious anemia gastric juice was resistant to further proteolysis. Cobalamin-specific R binder, perhaps produced in vivo by the action of refluxed pancreatic enzymes on swallowed R would preferentially bind ingested and/or biliary cobalamin rather than analogue and thereby could play a role in hastening the development of cobalamin deficiency in pernicious anemia.

Anemia↗