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Biomedical subjects

D M Novick

Publications and source records attributed to D M Novick.

54 records · Page 3Linked to original sources

Hepatitis B virus DNA in saliva, urine, and seminal fluid of carriers of hepatitis B e antigen.

Concentrated samples of saliva, urine, and seminal fluid from 23 men with chronic liver disease who were positive for hepatitis B e antigen were examined for the presence of hepatitis B virus deoxyribonucleic acid (HBV-DNA) by molecular hybridisation. HBV-DNA was detected in saliva from 15 of 17 men (88%), urine from 12 of 22 men (55%), and seminal fluid from 13 of 21 men (62%). The presence of hepatitis B virus in such secretions has important epidemiological implications for heterosexual and homosexual contact.

Autoradiography↗

Hepatitis D virus antibody in HBsAg-positive and HBsAg-negative substance abusers with chronic liver disease.

The hepatitis D virus (HDV; previously called the "delta agent") is a defective organism which can replicate only in the presence of the hepatitis B virus (HBV). We tested the serum of 95 substance abusers, all of whom had sufficient evidence of chronic liver disease to warrant a liver biopsy, for hepatitis D virus antibody (anti-HDV). Anti-HDV was detected in five of eight hepatitis B surface antigen (HBsAg)-positive patients and 12 of 87 (14%) HBsAg-negative patients. Antibody to the hepatitis B core antigen (anti-HBc) was the sole hepatitis B marker in eight of the 12 (67%) anti-HDV-positive, HBsAg-negative patients but in only 14 of 75 (19%) anti-HDV-negative, HBsAg-negative patients (P less than 0.005). None of the anti-HDV-positive, HBsAg-negative patients had detectable IgM anti-HBc in the serum or hepatitis D antigen in liver tissue, and they had similar clinical features and liver biopsy diagnoses to HBsAg-negative patients without anti-HDV. We conclude that anti-HDV in HBsAg-negative substance abusers reflects infection with HDV and HBV in the distant past and does not indicate more severe liver disease than that seen in HBsAg-negative patients without anti-HDV.

Adult↗

Diminished responsiveness of homosexual men to antiviral therapy for HBsAg-positive chronic liver disease.

To identify factors predicting response to antiviral therapy, we reviewed the clinical features of 38 male hepatitis B surface antigen (HBsAg) carriers who received adenine arabinoside or lymphoblastoid interferon. All patients were followed for one year or longer. Response was defined as loss of hepatitis B e antigen, hepatitis B virus DNA and DNA polymerase from the serum. Only 2 of 19 (11%) homosexual men responded, compared with 10 of 19 (53%) heterosexual men (P less than 0.02). Both responders in the homosexual group had received lymphoblastoid interferon. None of the 13 homosexual men, but 8 of 16 heterosexual men, responded to adenine arabinoside or its monophosphate (P less than 0.01). Responders to antiviral therapy had higher (P less than 0.05) serum levels of aspartate aminotransferase (median 115, range 51-344) than did non-responders (median 83, range 32-181). The decreased responsiveness of homosexual men to antiviral therapy may be a result of more severe immunologic abnormalities in homosexual than in heterosexual men with HBsAg-positive chronic liver disease.

Adult↗

Hepatic cirrhosis in young adults: association with adolescent onset of alcohol and parenteral heroin abuse.

Hepatic cirrhosis is infrequently diagnosed in young adults. In a hospital for addictive diseases in New York City, we found cirrhosis in 53 patients under age 35 within just 40 months. The cirrhosis was biopsy-proven in 37 patients (group I) and diagnosed clinically in 16 patients with severe liver disease (group II). Alcohol abuse was found in 51 patients (96%), and parenteral heroin abuse was seen in 52 (98%). The duration of alcohol abuse was seven or fewer years in 24 patients (45%) and 10 or fewer in 39 (74%). In 44 (83%), the substance abuse began in adolescence. Comparison of group I cirrhotic patients with 65 non-cirrhotic biopsied patients showed that cirrhosis was significantly associated with abuse of both alcohol and parenteral heroin (p less than 0.001). The distribution of 66 HLA antigens from A, B, C, and DR loci showed no differences when 42 patients were compared with 42 ethnically-matched control substance abusers. The early development of cirrhosis in these young patients may be related to multiple hepatic injuries induced by alcohol and parenteral heroin abuse and to the onset of addictive diseases during adolescence or early adult life.

Adult↗

Abuse of antibiotics by abusers of parenteral heroin or cocaine.

We studied antibiotic intake in 197 abusers of alcohol, sedatives, or parenteral heroin or cocaine. Thirteen patients, all abusers of parenteral heroin or cocaine, had taken antibiotics without prescription, obtained from friends, from old prescriptions, or by purchase on the street. Past or present street purchase of antibiotics was noted in 27 patients and was more common (P less than .02) in parenteral substance abusers. Four parenteral substance abusers had infection or colonization with methicillin-resistant Staphylococcus aureus, and three of them had purchased antibiotics on the street before the present or a recent past hospitalization. Physicians treating abusers of parenteral heroin or cocaine should be aware that such patients may be taking antibiotics without medical supervision. This practice may be an important factor in the development and spread of methicillin-resistant S aureus.

Anti-Bacterial Agents↗

Major medical problems and detoxification treatment of parenteral drug-abusing alcoholics.

Patients with combined addictive disease are frequently encountered in New York City. Three detoxification schedules have been developed which, alone or in combination, may be used for almost all substance abusers who require pharmacologic detoxification. Numerous factors contribute to pathogenesis of infections in parenteral drug-abusing alcoholics, including aspiration, impaired pulmonary function, immunologic abnormalities, and changes in endogenous microbial flora. The acquired immunodeficiency syndrome (AIDS) has recently emerged as a serious medical complication of parenteral substance abuse. Liver disease in parenteral drug-abusing alcoholics is also multifactorial. The direct hepatotoxic effects of alcohol, the adulterants of illicit, injectable drugs, and infections with the hepatitis B virus, non-A, non-B viruses, and the delta agent may all be contributing factors.

Acquired Immunodeficiency Syndrome↗

Methadone disposition in patients with chronic liver disease.

Chronic liver disease is common in methadone-maintained patients. We studied the disposition of this drug in 14 patients with biopsy-proved chronic liver disease and five otherwise healthy subjects receiving methadone maintenance treatment. The patients were divided into three groups based on the severity of liver disease, with group I having the most severe disease. The apparent terminal half-life of methadone was longer in group I than in group II and III (moderate and mild chronic liver disease, P less than 0.01) and the contrast group (P less than 0.05). All other kinetic indices determined for group I and all kinetic indices in groups II and III were essentially the same as those in the contrast subjects or in the other patient groups. Seven patients, including al five in group I, had flattened plasma methadone concentration-time curves. The data suggest that the maintenance dosage of methadone need not be changed in stable chronic liver disease.

Administration, Oral↗

Hepatitis B serologic studies in narcotic users with chronic liver disease.

Hepatitis B surface antigen (HBsAG) and antibody (anti-HBs), and antibody to the hepatitis B core antigen ( anti-HBc) were measured by radioimmunoassay in 46 current or former narcotic users who underwent liver biopsy for evaluation of chronic liver disease. Significant alcohol abuse was found in 38 narcotic users (82.6%). On liver biopsy, 24 had cirrhosis (52.2%), nine had chronic active hepatitis (19.6%), five had lipid accumulation (10.9%) and eight had other diagnoses (17.4%). At least one marker for hepatitis B was found in 45 of 46 narcotic users (97.8%). Five had HBsAg and anti HBc (10.9%), one had anti-HBs alone (2.2%), 30 had anti-HBs and anti-HBc (65.2%) and nine had anti-HBc alone. Although almost all narcotic users with chronic liver disease have active or resolved hepatitis B infection, alcohol abuse appears to be the major factor in the development of cirrhosis in the subset of narcotic users studied.

Adult↗

A randomized study of the effects of adenine arabinoside 5'-monophosphate (short or long courses) and lymphoblastoid interferon on hepatitis B virus replication.

A previous randomized controlled study has shown a 30% rate of HBe antigen/antibody seroconversion within 1 year of a month course of adenine arabinoside-5'-monophosphate; no seroconversion occurred in the control group. In this study of patients derived from the same population, 45 hepatitis B virus carriers with chronic liver disease were randomized to receive either a short (4-week) course of adenine arabinoside-5'-monophosphate, a long (7 to 8-week) course of adenine arabinoside-5'-monophosphate or a 12-week course of lymphoblastoid interferon. Long-lasting suppression of hepatitis B virus replication with disappearance of serum hepatitis B virus DNA and clearance of HBeAg occurred within 12 months of treatment in four patients who received the short course of adenine arabinoside-5'-monophosphate and in five who received interferon. Of the nine responders, four also lost HBsAg. A response to antiviral therapy was accompanied by clinical and biochemical evidence of improvement in liver disease. None of the patients who received a long course of adenine arabinoside-5'-monophosphate responded. Peripheral neuropathy and myalgia were the most serious adverse effect affecting three recipients of the short course of adenine arabinoside-5'-monophosphate and eight recipients of the long course. Thrice weekly administration of interferon was well-tolerated. Further studies to identify the characteristics of the "responder patients" and large-scale controlled trials of antiviral therapy in these subgroups are indicated.

Adult↗

Effect of severe alcoholic liver disease on the disposition of methadone in maintenance patients.

We studied methadone disposition in 11 maintenance patients with alcoholic liver disease of such severity that liver biopsy was contraindicated. Nine methadone-maintained patients with recent alcohol abuse but minimal or no evidence of liver disease served as controls. Most kinetic indices, including the apparent oral clearance and area under the concentration-time curves, were similar in patients and controls. Although the apparent terminal half-life of methadone was longer (p = 0.04) in the patients with liver disease, the peak plasma methadone level was lower (p = 0.03). None of the patients had signs or symptoms of methadone overdosage or abstinence at the time of study. Six patients and one control had flattened plasma methadone concentration-time curves. We hypothesize that, in severe liver disease, damage to hepatic drug-metabolizing systems is offset by damage to the capacity of the liver to store and release unchanged methadone. The usual methadone maintenance dose may be continued in stable patients with severe alcoholic cirrhosis.

Adult↗

Methadone medical maintenance (MMM): treating chronic opioid dependence in private medical practice--a summary report (1983-1998).

BACKGROUND: Methadone Medical Maintenance (MMM) was implemented in 1983 to enable socially rehabilitated methadone patients to be treated in the offices of private physicians rather than in the traditional clinic system. Over a period of 15 years, 158 methadone patients who fulfilled specific criteria within the clinic system entered this program in New York City. Participating patients reported to their physician once a month and received a one-month supply of methadone tablets rather than a one-day liquid dose in a bottle. METHOD: Of the 158 patients who entered this program, 132 (83.5%) were compliant with the regulations and proved to be treatable within the hospital-based private practices of internists participating in the program. Compliant MMM patients found it easier to improve their employment status and business situations, finish their educations, and normalize their lives in MMM as opposed to the traditional clinic system because they had simplified reporting schedules and fewer clinical restrictions. Twelve (8%) compliant patients were able to successfully withdraw from methadone after an average of 17.7 years of treatment in both the traditional clinics and MMM. Twenty compliant patients (13%) died from a variety of causes, 40% of which were related to cigarette smoking. None of the deaths were attributable to long-term methadone treatment. Other causes of death included hepatitis C, AIDS, cancer, homicide, complications of morbid obesity and meningitis. RESULTS: The 26 noncompliant patients (16.5%) were referred back to their clinics for continued treatment or were discharged for failure to report as directed. A major cause of failure in MMM was abuse of crack/cocaine. CONCLUSIONS: Stigma concerning enrollment in methadone treatment was a major social issue that patients faced. Many refused to inform employers, members of their families, friends, and other physicians who treated them for a various of conditions that they were methadone patients. The methadone medical maintenance physician, therefore, functions as a medical ombudsman for the patient, educating other physicians who treat the patient about methadone maintenance and its applicability to the patient. Our results can serve as a model for the expansion of office-based MMM treatment.

Adult↗

The impact of hepatitis C virus infection on methadone maintenance treatment.

Hepatitis C virus infection is now recognized as a common and serious complication of injection drug use and will be encountered frequently in methadone maintenance patients. Approximately 1.8% of the United States population, or 3.9 million persons, are infected with hepatitis C virus. A majority of acute hepatitis C virus infections are associated with injection drug use, and 64-88% of injection drug users in seroprevalence studies have antibodies to hepatitis C. Hepatitis C virus infection is almost always chronic, and alcohol use increases the clinical severity. Therapy with interferon and ribavirin will induce long-term remission in up to 43% of patients with hepatitis C virus infection. Proper diagnosis and treatment of hepatitis C virus infection will be indicated for many patients in methadone programs and will require considerable resources.

Alcoholism↗

Acquired immunodeficiency syndrome and infection with hepatitis viruses in individuals abusing drugs by injection.

The abuse by injection of heroin or other drugs has long been associated with liver disease caused by hepatitis B virus (HBV) and other viruses. Increasingly severe hepatic and virological complications of parenteral drug abuse have been reported due to infection with new viruses or concomitant alcohol abuse. The hepatitis delta virus (HDV) can replicate and cause liver infection only in the presence of HBV; such infection in HBV carriers may cause rapidly progressive and clinically significant liver disease. Liver cirrhosis is frequently detected in parenteral drug abusers who have chronic infection with both HBV and HDV or who also abuse alcohol. More than one quarter of those persons with acquired immunodeficiency syndrome (AIDS) in the United States of America are homosexual or heterosexual males who are parenteral drug abusers. Existing evidence implicates parenteral drug abusers in the spread of hepatitis viruses and the retrovirus associated with AIDS to the general population. To cope with these serious problems the authors suggest that more intensive international co-operation is needed, particularly with a view to promoting data collection, research and the exchange of knowledge and experience on measures that have been effective in dealing with parenteral drug abuse and its complications.

Acquired Immunodeficiency Syndrome↗