Changing disease patterns and their significance in the training of undergraduate and postgraduate students.
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Biomedical subjects
Publications and source records attributed to J Greenspan.
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BACKGROUND: Congenital diaphragmatic hernia (CDH) has been cited to have a mortality rate of 50%. There have been multiple studies at individual institutions demonstrating potential benefits from various strategies including extracorporeal life support (ECLS), delayed repair, and lower levels of ventilator support. There has been no multicenter survey of institutions offering these modalities to describe the current use of ECLS and survival of these infants. In addition, the relationship between the number of patients with CDH managed at an individual institution and outcome has not been evaluated. METHODS: We queried 16 level III neonatal intensive care centers on the use of ECLS and survival of infants with CDH who were treated during 2 consecutive years (1993 to 1995). Data are presented as mean +/- SEM, median, and range. RESULTS: Data were collected on 411 patients. Of these, 71% +/- 8% were outborn and 8% +/- 3% were considered nonviable. Overall survival of CDH infants was 69% +/- 4% (range, 39% to 95%). The survival rate of infants on ECLS was 55% +/- 4%, whereas survival of infants not requiring ECLS was significantly increased at 81% +/- 5% (p = 0.005). The mean rate of ECLS use was 46% +/- 2%. There was no correlation between the number of cases per year at an individual institution and overall survival, ECLS survival, or ECLS use (r = 0.341, 0.305, and 0.287, respectively). There was also no correlation between case volume at an individual institution and ECLS survival (r = 0.271). CONCLUSIONS: The current survival rate and rate of ECLS use in infants with CDH at level III neonatal intensive care units in the United States are 69% +/- 4% and 46% +/- 2%, respectively. There is no correlation between the yearly individual center experience with managing CDH and rate of ECLS use or outcome.
This study evaluates the effect of maternal depression on neonatal health status in premature infants during their initial hospitalization. Infants younger than 34 weeks' gestation born to nondrug abusing mothers were enrolled in the study. Thirty-one mother-infant pairs were identified. Maternal depression was evaluated by the Center for Epidemiologic Studies-Depression Scale (CES-D). Scores > or = 16 defined maternal depression. Initial infant physiologic health status was determined by the Score for Neonatal Acute Physiology (SNAP). In-hospital health status was assessed by the following variables: days receiving supplemental oxygen, days on mechanical ventilation (VENT), and days not on enteral feeding (NPO). Health status variables evaluated for long-term outcome included bronchopulmonary dysplasia at 28 days (BPD), BPD at 34 weeks' postmenstrual age (BPD-34), and intraventricular hemorrhage (IVH). Seventeen (55%) of 31 mothers manifested depression on the CES-D. No epidemiologic differences were found between this group and the nondepressed mothers. No differences in gestation or birth weight was detected between the preterm infants of depressed versus nondepressed mothers. The CES-D scores correlated significantly with SNAP (r = .36, P < .02). Infants of depressed mothers experienced significantly worse outcomes in the occurrence of BPD (P = .015), BPD-34 (P = .049), and IVH (P = .055). This study confirms that maternal depression occurs frequently in mothers of preterm infants and adversely affects the presenting neonatal health status of their babies during the initial hospitalization. Maternal depression was related to the severity of the initial neonatal illness and was significantly related to IVH and BPD. These factors may have long-term consequences for subsequent growth, neurodevelopment, and recurrence of related health problems.
Sitosterolemia is a genetic disorder characterized by sitosterol accumulation in plasma and clinically accelerated atherosclerosis. Under a condition of metabolic control with a 30% fat, low-sitosterol diet, we compared the effects of monotherapy and dual-drug treatment with lovastatin and cholestyramine on plasma sterol parameters and endogenous cholesterol synthesis in a homozygous sitosterolemic patient with concomitant heterozygous familial hypercholesterolemia (FH), her obligate heterozygous father, and hyperlipidemic control subjects. We found that for both the sitosterolemic homozygote and heterozygote, cholestyramine plus lovastatin dual therapy proved not to be superior to either drug treatment alone. In the homozygous patient, cholestyramine accounted for the decrease of plasma sterol (ie, lovastatin was ineffective), whereas in the heterozygote, lovastatin represented the margin of difference (ie, low-dose cholestyramine was relatively ineffective). Thus, the best treatment option for this homozygote child and her heterozygote father appears to be monotherapy with cholestyramine and lovastatin, respectively. Stimulation by bile acid malabsorption produced a dramatic decrease of plasma sterols in the homozygote, without increasing endogenous cholesterol synthesis, but this therapy was ineffective in the heterozygote. Decreasing endogenous cholesterol synthesis with lovastatin was effective in the heterozygote, but ineffective in the homozygote. In suspected sitosterolemia, a poor sterol response to lovastatin and a dramatic response to cholestyramine may differentiate homozygous from heterozygous and other familial forms of hyperlipidemia.
Oxygen consumption at intermittent mandatory ventilation (IMV) rates of 10 and 20 breaths per minute was evaluated to determine whether a higher IMV rate in mechanically ventilated premature infants with apnea and respiratory insufficiency would reduce metabolic expenditure. Ten studies were performed in seven infants, with three infants studied twice after a trial of failed elective extubation. The mean birth weight was 952 +/- 183 kg (SD), and the mean postnatal age was 12 +/- 8 days (SD). Mean oxygen consumption per kilogram of body weight was not significantly related to pulmonary resistance, dynamic lung compliance, or resistive work of breathing. Mean oxygen consumption was not altered at the different IMV rates. The oxygen consumption difference at the two IMV rates was not significantly related to dynamic lung compliance, resistance, or work of breathing. These results demonstrate that mechanically dependent premature infants without bronchopulmonary dysplasia do not have significant alteration in oxygen consumption with changes in IMV. This finding suggests that there is no potential metabolic energy balance benefit in use of moderately higher IMV rates to achieve improved growth rates in this population of infants.
Previous reports cite optimization of O2 delivery (DO2) to 660 mL/min/m2, O2 consumption (VO2) to 170 mL/min/m2, and cardiac index (CI) of 4.5 L/min as predicting survival. We prospectively evaluated 76 consecutive patients with multiple trauma admitted directly to the ICU from the operating room or emergency department. Patients had serum lactate levels and oxygen transport measured on ICU admission and at 8, 16, 24, 36, and 48 hours. Patients were analyzed with respect to survival (S) versus nonsurvival (NS), lactate clearance to normal (< or = 2 mmol/L) by 24 and 48 hours, hemodynamic optimization as defined above, as well as Injury Severity Score (ISS), ICU stay (LOS), and admission blood pressure. All patients achieved non-flow-dependent VO2. There was no difference in CI, DO2, VO2, or ISS when S was compared with NS. All 27 patients whose lactate level normalized in 24 hours survived. If lactate levels cleared to normal between 24 and 48 hours, the survival rate was 75%. Only 3 of the 22 patients who did not clear their lactate level to normal by 48 hours survived. Ten of the 25 nonsurvivors (40%) achieved the above arbitrary optimization criteria. Fifteen of the survivors never achieved any of these criteria. Optimization alone does not predict survival. However, the time needed to normalize serum lactate levels is an important prognostic factor for survival in severely injured patients.
Gender and dietary saturated fat remain two strong predictors of coronary heart disease susceptibility. In a retrospective meta-analysis of five studies, we analyzed the impact of gender and diet composition on lipoprotein change, or 'response' (delta) in 63 normolipidemic subjects fed two contrasting, metabolically controlled diets. One diet had a low polyunsaturated to saturated fatty acid ratio (low P:S) and the second, a high P:S ratio in a crossover design. Lipid profile 'responsiveness' was calculated as the adjusted difference (mg/dl) following each diet period. Multivariate analysis of variance revealed that triglyceride (delta TG), very low density (delta VLDL-C), and high density lipoprotein cholesterol responses (delta HDL-C) were the only statistically significant, gender-specific lipid responders. Difference in low density lipoprotein (LDL-C) response to diet was similar between the sexes. Multiple regression analysis identified the independent predictors of delta HDL-C for males and females. In females, the HDL-C lowering was predicted by the percentage increase in polyunsaturated fatty acids, baseline HDL-C levels and, inversely by delta TG. The male predictor of delta HDL-C was diet alone (replacement of saturated fat by dietary polyunsaturated fatty acids). Results showed that while normolipidemic males and females show similar reductions in LDL-C following dietary change, delta HDL-C is gender-specific, with females showing a greater fall in the potentially 'beneficial' HDL-C than males. We conclude that a diet crossover may be of less benefit to normolipidemic females than to males, due to HDL-C lowering. Gender and diet may both become pivotal considerations in achieving plasma lipid goals.
Aphthous stomatitis is a common, recurrent, painful ulcerative condition of the oral mucosa. Cigarette smoking has been reported to protect against aphthous ulcers. To determine whether smokeless tobacco use also protects against aphthous ulcers, we examined the oral mucosa in 1456 professional baseball players, about half of whom were smokeless tobacco (ST) users. After controlling for the confounding effects of age, race, cigarette smoking, alcohol consumption, and dental hygiene practices, ST use was found to significantly reduce the risk of aphthous ulcers among these healthy young men (odds ratio = 0.4; p = 0.04). It has been suggested that cigarette smoking prevents aphthous ulcers by causing increased keratinization of the oral mucosa, and ST may protect by the same mechanism. Alternatively, a component of tobacco that is systemically absorbed might be responsible for protecting against aphthous ulcers. If the mechanism that protects ST users against aphthous ulcers is systemic, then nicotine is the likely protective factor.
Serologic assays for human T cell lymphotropic virus types I and II (HTLV I/II) infection were done in 676 intravenous drug users (IVDUs) in San Francisco between 1985 and 1987: 150 in 1985, 44 in 1986, and 482 in 1987. All sera were tested by Western blot, ELISA, and p24 RIA. A total of 111 participants were seropositive in a minimum of two assays. Duration of intravenous heroin use was strongly associated with the risk of HTLV I/II seropositivity: greater than or equal to 21 years odds ratio, 6.1 (95% confidence interval [CI], 2.2-17.5), compared with less than 10 years of heroin use. Additional independent risk factors included black or Hispanic race, female sex, and the use of drugs in a shooting gallery. Coinfection of HTLV I/II and human immunodeficiency virus was less frequent than expected by chance (P less than .02). Longitudinal specimens were available in 154 participants. The age- and race-adjusted seroconversion rate was 3.4% (95% CI, 1.3-8.9) per person per year. Of the 349 homosexual men tested, none were HTLV I/II-seropositive.
The risk for oral mucosal lesions associated with use of smokeless tobacco among 1,109 professional baseball players during spring training in 1988 was investigated. Leukoplakia was very strongly associated with use of smokeless tobacco in this population of healthy young men. Of the 423 current smokeless tobacco users, 196 had leukoplakia compared to seven of the 493 nonusers (OR = 60.0, 95% CI = 40.5-88.8). The amount of smokeless tobacco used (in hours per day that smokeless tobacco was held in the mouth), recency of smokeless tobacco use (hours since last use), type (snuff versus chewing tobacco), and brand of snuff used were significantly associated with risk for leukoplakic lesions among smokeless tobacco users. Ninety-eight leukoplakic areas in 92 subjects were biopsied and examined microscopically. All lesions were benign, but one specimen had mild epithelial dysplasia. The long-term significance of leukoplakia in smokeless tobacco users and their relation to oral cancer is not clear.
Investigation into a possible role of several human viruses, including human cytomegalovirus (HCMV), human immunodeficiency virus (HIV-1), hepatitis B virus (HBV), human herpesvirus 6 (HHV6), and Epstein-Barr virus (EBV) in the pathogenesis of Kaposi's sarcoma (KS) has resulted in the lack of an association of these viruses in KS biopsy and cloned KS cell line specimens. Since nearly all patients with KS, including those with HIV-associated KS, have a high incidence of HCMV infection, HCMV has been proposed to be etiologically associated with KS. Moreover, our previous studies showed the retention of HCMV morphological transforming region II (mtrII) in both transformed and tumor-derived cell lines. As a result, we focused on the nucleic acid hybridization analysis of both KS biopsies from AIDS patients as well as cloned KS endothelial cell lines for HCMV mtrII sequences. We also analyzed KS biopsy and KS cloned cell line specimens for HIV-1, HBV, HHV6, and EBV sequences, since these viruses have also been implicated in the etiology of KS. In one set of experiments, Southern blot analysis revealed the presence of HCMV mtrII sequences in two of six KS biopsies; in other experiments, HBV sequences were found in one of seven KS biopsies. No hybridization in any biopsy tissue was detected for HIV-1 DNA sequences. The analysis of six independently derived cloned KS cell lines was next studied. All these lines were negative for hybridization to the HCMV mtrII transforming fragment as well as to subgenomic fragments of HHV6 and EBV.(ABSTRACT TRUNCATED AT 250 WORDS)
Diagnosis of carpal tunnel syndrome is based on a thorough patient history, careful physical examination, and provocative testing. Electrophysiologic testing should be completed before treatment is begun. Conservative therapy is appropriate first-line treatment unless the condition is severely advanced or immediate resolution of symptoms is essential. I recommend use of wrist splints, steroid injection, nonsteroidal antiinflammatory drugs, and pyridoxine, followed by reexamination in three weeks, or earlier if symptoms progress. For persistent or acute symptoms, surgical treatment may be necessary.
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The efficacy of an educational intervention designed to improve dentists' knowledge, attitudes, and behaviors about acquired immune deficiency syndrome (AIDS) was tested. The intervention had three components: computerized feedback comparing participants' own knowledge, attitudes, and behaviors with those of fellow participants and with an ideal; periodic bulletins; and telephone conference calls with experts. The group receiving the educational package had better scores than a control group on outcomes of willingness to treat persons with AIDS; identification of human immunodeficiency virus lesions; knowledge of AIDS; and completeness of both intraoral and extraoral examinations. It was concluded that intervention is one approach to increasing dentists' positive response to the AIDS epidemic.
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A young woman who developed acute pancreatitis coincident with Crohn's disease is presented. The pancreatitis was documented by pancreatic hyperamylasemia, elevated urine amylase activity, abdominal sonogram, computed tomography, and laparotomy. A cause-and-effect relationship has not been established, however; no etiology other than the Crohn's disease, which was confined to the ileum and colon, could be identified. Surgical removal of the severely involved ileum led to the resolution of the pancreatitis. A possible relationship between acute pancreatitis and Crohn's disease is proposed, although potential pathophysiologic mechanisms are unknown. The diagnosis of pancreatic involvement in such cases may make an important contribution to therapy.
There has been a relative lack of literature on the association of hypohidrosis in Sjögren's syndrome with any lesion having specific histologic findings. We looked at a recent case presentation of a 55-year-old man with complaints of dry mouth and dry eyes, becoming easily overheated in direct sunlight, and having difficulty in perspiring. Physical examination showed fissuring and atrophy of the tongue and angular cheilitis. A punch biopsy of the skin showed a moderate number of eccrine gland and ductal structures in the lower reticular dermis, each surrounded by a dense cellular infiltrate of plasma and lymphocytic cells. Our patient also had a markedly decreased sweating response to methacholine. In reviewing the literature as far back as 1951 and on the basis of findings in our present case study, we conclude that it seems probable that the severity of the skin disease is an important determining factor in predicting whether the sweat gland lesion does exist.
Infections caused by species within the viridans streptococci have been associated with different clinical characteristics. We studied 36 patients with viridans streptococcal endocarditis. Complications were seen in 10 (32%) of 31 patients with native valve endocarditis and four (80%) of five with prosthetic valve endocarditis and included death in two, valve replacement in six, persistent infection in three, emboli in two, and congestive heart failure in nine. Two-dimensional echocardiograms demonstrated vegetations in 26 (72%) of 36, flail mitral valves in seven, disruption of aortic valve prosthesis in one, and perivalvular abscesses in three (two Streptococcus sanguis I and one Streptococcus intermedius I). All twelve patients with native valve endocarditis who suffered complications had vegetations detected by two-dimensional echocardiography, whereas seven patients with native valve endocarditis without vegetations, as detected by two-dimensional echocardiography, had no complications (P = .03). We found no significant correlation between streptococcal species and clinical outcome. To confirm our identifications, we sent 16 identical viridans streptococcal endocarditis isolates to five institutions; only three of 16 were identified as the same species by all five institutions. We conclude that viridans streptococcal endocarditis can be associated with a virulent clinical course and that there is marked variability in species designations of individual strains by different laboratories.