The feasibility, usability, and clinical utility of traditional paper food and symptom journals for patients with irritable bowel syndrome.

BACKGROUND: Paper food and gastrointestinal (GI) symptom journals are used to help irritable bowel syndrome (IBS) patients determine potential trigger foods. The primary aim of this study was to evaluate the feasibility, usability, and clinical utility of such journals as a data collection tool. A secondary aim was to explore a method for analyzing journal data to describe patterns of diet and symptoms. METHODS: Participants (N=17) were asked to log three sets of 3-day food and symptom journals over a 15-day period. Feasibility was evaluated by journal completion rates, symptom logging compliance, and logging fatigability. The feasibility, usability, and clinical utility of journaling were also assessed by a customized evaluation and exit interview. For each journal, regression analyses were conducted to examine relationships between key meal nutrients and subsequent symptoms. KEY RESULTS: Most participants were young (mean age 35±12) Caucasian (N=13) women (N=14). Journal completion rates were 100% for all participants with no logging fatigability. Over half perceived paper journaling of food and symptoms as feasible, usable, and clinically useful. Thirteen participants demonstrated a strong association with at least one symptom and meal nutrient. Patterns of associations differed among participants. CONCLUSIONS AND INFERENCES: Paper journaling of food and GI symptoms for 9 days over a 15-day period appeared to be a feasible and usable data collection tool for IBS patients. Over half perceived journaling as at least somewhat clinically useful. Findings from this study support the anecdote that food trigger(s) and associated symptom(s) vary for each individual.

Can self-administered questionnaires supplant objective testing of erectile function? A comparison between the International Index Of Erectile Function and objective studies.

To determine whether the results of the self-reported International Index of Erectile Function (IIEF) to assess erectile function can overestimate the degree of erectile impairment. A total of 32 consecutive patients seeking treatment for erectile dysfunction (ED) at a urologist's office were evaluated by completion of the erectile function domain of the IIEF. Nocturnal penile tumescence testing using the Rigiscan (Timm Medical Technologies Inc., USA) was performed in these patients after completion of the IIEF. The median IIEF-6 score was 9 of 30 (range, 1-25; mean, 11/30). Rigiscan results were abnormal in six patients (19%), normal in 25 patients (78%), and unable to interpret in one patient (3%). IIEF-6 scores were subdivided by severity along with Rigiscan results. There was no correlation between age, IIEF score, or Rigiscan results. In conclusion, the IIEF is a useful tool and is helpful for follow-up of a patient to evaluate efficacy of treatments for ED, but should not replace objective testing to diagnose the quality of ED.

Pentosidine formation in skin correlates with severity of complications in individuals with long-standing IDDM.

Pentosidine is an advanced glycosylation end product and protein cross-link that results from the reaction of pentoses with proteins. Recent data indicate that long-term glycation of proteins with glucose also leads to pentosidine formation through sugar fragmentation. In this study, the relationship between the severity of diabetic complications and pentosidine formation was investigated in collagen from skin-punch biopsies from 25 nondiabetic control subjects and 41 IDDM patients with diabetes duration greater than 17 yr. Pentosidine was significantly elevated in all IDDM patients versus control subjects (P less than 0.0001). It correlated strongly with age (P less than 0.0001) and weakly with duration (P less than 0.082). Age-adjusted pentosidine levels were highest in grade 2 (severe) versus grade 1 and 0 complication in all four parameters tested (retinopathy, proteinuria, arterial stiffness, and joint stiffness). Significant differences were found for retinopathy (P less than 0.014) and joint stiffness (P less than 0.041). The highest degree of association was with the cumulative grade of individual complication (P less than 0.005), determined by summing indexes of all four parameters. Pentosidine also was significantly elevated in the serum of IDDM patients compared with control subjects (P less than 0.0001), but levels were not significantly correlated with age, diabetes duration, complication, or skin collagen pentosidine (P greater than 0.05). A high correlation between pentosidine levels and long-wave collagen-linked fluorescence also was observed, suggesting that pentosidine is a generalized marker of accelerated tissue modification by the advanced glycosylation/Maillard reaction, which is enhanced in IDDM patients with severe complications.

Chromatographic quantitation of plasma and erythrocyte pentosidine in diabetic and uremic subjects.

Pentosidine is a fluorescent advanced Maillard/glycosylation product and protein cross-link present in elevated amounts in skin from diabetic and uremic subjects. A high-performance liquid chromatographic (HPLC) assay was developed to quantitate pentosidine in plasma and erythrocytes and other tissue proteins with low levels of pentosidine. High protein content and presence of basic amino acids and O2 during acid hydrolysis led to the formation of fluorescent artifacts that could be separated from true pentosidine through combined reverse-phase ion-exchange HPLC. No true pentosidine was formed during acid hydrolysis of ribated protein, suggesting that Amadori products do not generate artifactual pentosidine during hydrolysis. With the combined reverse-phase ion-exchange chromatographic assay, we found a 2.5-fold (P less than 0.001) and a 23-fold (P less than 0.001) elevation of mean +/- SD plasma protein pentosidine in diabetic (2.4 +/- 1.2 pmol/mg) and uremic (21.5 +/- 10.8 pmol/mg) subjects compared with healthy (0.95 +/- 0.33 pmol/mg) subjects. Pentosidine in hemolysate was normal in diabetes but dramatically elevated in uremia (0.6 +/- 0.4 pmol/mg hemoglobin, P less than 0.001). Although the precise nature of the pentosidine precursor sugar is unknown, plasma pentosidine may be a useful marker for monitoring the biochemical efficacy of trials with aminoguanidine or other treatment modalities. Furthermore, pentosidine in plasma proteins may act as a signal for advanced glycosylation end product-mediated receptor uptake by macrophages and other cells and contribute to accelerated atherosclerosis in diabetes and uremia.

Evidence of a glycemic threshold for the formation of pentosidine in diabetic dog lens but not in collagen.

The relationship between long-term glycemic control and the advanced Maillard reaction was investigated in dura mater collagen and lens proteins from dogs that were diabetic for 5 years. Diabetic dogs were assigned prospectively to good, moderate, and poor glycemic control and maintained by insulin. Biochemical changes were determined at study exit. Mean levels of collagen digestibility by pepsin decreased (NS) whereas collagen glycation (P < 0.001), pentosidine cross-links (P < 0.001), and collagen fluorescence (P = 0.02) increased with increasing mean HbA1 values. Similarly, mean levels of lens crystallin glycation (P < 0.001), fluorescence (P < 0.001), and the specific advanced lens Maillard product 1 (LM-1) (P < 0.001) and pentosidine (P < 0.005) increased significantly with poorer glycemic control. Statistical analysis revealed very high Spearman correlation coefficients between collagen and lens changes. Whereas pentosidine cross-links were significantly elevated in collagen from diabetic dogs with moderate levels of HbA1 (i.e., 8.0 +/- 0.4%), lens pentosidine levels were normal in this group and were elevated (P < 0.001) only in the animals with poor glycemic control (HbA1 = 9.7 +/- 0.6%). Thus, whereas protein glycation and advanced glycation in the extracellular matrix and in the lens are generally related to the level of glycemic control, there is evidence for a tissue-specific glycemic threshold for pentosidine formation, i.e., glycoxidation, in the lens. This threshold may be in part linked to a dramatic acceleration in crystallin glycation with HbA1 values of > 8.0% and/or a loss of lens membrane permeability. This study provides support at the molecular level for the growing concept that glycemic thresholds may be involved in the development of some of the complications in diabetes.

Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Control and Complications Trial.

The relationships between long-term intensive control of glycemia and indicators of skin collagen glycation (furosine), glycoxidation (pentosidine and N(epsilon)-[carboxymethyl]-lysine [CML]), and crosslinking (acid and pepsin solubility) were examined in 216 patients with type 1 diabetes from the primary prevention and secondary intervention cohorts of the Diabetes Control and Complications Trial. By comparison with conventional treatment, 5 years of intensive treatment was associated with 30-32% lower furosine, 9% lower pentosidine, 9-13% lower CML, 24% higher acid-soluble collagen, and 50% higher pepsin-soluble collagen. All of these differences were statistically significant in the subjects of the primary prevention cohort (P < 0.006-0.001) and also of the secondary intervention cohort (P < 0.015-0.001) with the exception of CML and acid-soluble collagen. Age- and duration-adjusted collagen variables were significantly associated with the HbA1c value nearest the biopsy and with cumulative prior HbA1c values. Multiple logistic regression analyses with six nonredundant collagen parameters as independent variables and various expressions of retinopathy, nephropathy, and neuropathy outcomes as dependent variables showed that the complications were significantly associated with the full set of collagen variables. Surprisingly, the percentage of total variance (R2) in complications explained by the collagen variables ranged from 19 to 36% with the intensive treatment and from 14 to 51% with conventional treatment. These associations generally remained significant even after adjustment for HbA1c, and, most unexpectedly, in conventionally treated subjects, glycated collagen was the parameter most consistently associated with diabetic complications. Continued monitoring of these subjects may determine whether glycation products in the skin, and especially the early Amadori product (furosine), have the potential to be predictors of the future risk of developing complications, and perhaps be even better predictors than glycated hemoglobin (HbA1c).

Cutaneous temperature measurements in men with penile prostheses: a comparison study.

To evaluate and compare the cutaneous temperature of the penis in normal men, those with erectile dysfunction (ED), those with semirigid penile prostheses (SRPPs), and those with inflatable penile prostheses (IPPs), and those before and after trimix injection to create a penile erection. A total of 68 patients were evaluated. Five patient groups were identified, including men with normal erectile function, with ED, with SRPPs, with IPPs, and following intracavernosal injection of trimix solution. Cutaneous glans temperature increased significantly by more than 2.2 degrees C in the trimix-injected group compared with all other groups (P<0.001). Using cutaneous temperature measurements of the penis, patients with SRPPs had significantly lower cutaneous glans temperatures than normals (P<0.02), those in the ED group (P<0.04), and those in the IPP-deflated group (P<0.01). The mean temperature difference was 1.44+/-0.40 degrees C. Using cutaneous temperature measurements of the penis, men with SRPPs have a colder glans as compared with men with normal erectile function, ED, IPPs, and those who have received an injection of trimix. Men with normal erectile function, ED, and IPPs did not have significant cutaneous temperature differences.

Addressing Inpatient Glycaemic Control with an Inpatient Glucometry Alert System.

Background. Poor inpatient glycaemic control has a prevalence exceeding 30% and results in increased length of stay and higher rates of hospital complications and inpatient mortality. The aim of this study was to improve inpatient glycaemic control by developing an alert system to process point-of-care blood glucose (POC-BG) results. Methods. Microsoft Excel Macros were developed for the processing of daily glucometry data downloaded from the Cobas IT database. Alerts were generated according to ward location for any value less than 4 mmol/L (hypoglycaemia) or greater than 15 mmol/L (moderate-severe hyperglycaemia). The Diabetes Team provided a weekday consult service for patients flagged on the daily reports. This system was implemented for a 60-day period. Results. There was a statistically significant 20% reduction in the percentage of hyperglycaemic patient-day weighted values >15 mmol/L compared to the preimplementation period without a significant change in the percentage of hypoglycaemic values. The time-to-next-reading after a dysglycaemic POC-BG result was reduced by 14% and the time-to-normalization of a dysglycaemic result was reduced from 10.2 hours to 8.4 hours. Conclusion. The alert system reduced the percentage of hyperglycaemic patient-day weighted glucose values and the time-to-normalization of blood glucose.

An unusual case of lung torsion.

We report a case of complete torsion of the right lung induced by transthoracic needle biopsy. While a delay in diagnosis occurred, viability of the torsed lung was maintained, thereby allowing for effective surgical repair.

Non-type b Haemophilus influenzae disease: clinical and epidemiologic characteristics in the Haemophilus influenzae type b vaccine era.

BACKGROUND: As a result of the decline in Haemophilus influenzae type b (Hib) disease caused by the widespread use of conjugate vaccines, non-type b H. influenzae will become a more important cause of H. influenzae (Hi) disease. Characterization of the clinical and epidemiologic features of non-b Hi disease is needed in the Hib vaccine era. METHODS: A prospective active surveillance study of invasive Hi disease involving pediatricians in the United Kingdom and Republic of Ireland. For the first phase of the study (October 1, 1992, to October 31, 1995) pediatricians were asked to report any child who had invasive Hi disease and who had received Hib conjugate vaccine. For the second phase of the study (November 1, 1995. To December 31, 1998) pediatricians were asked to report any child with invasive Hi disease regardless of vaccination status. RESULTS: During the study period 102 cases of invasive non-type b Hi disease and 106 cases of invasive Hib disease were reported in children who had been fully vaccinated against Hib. Children with non-type b disease were younger (16 vs. 22 months of age, P = 0.08), less likely to have meningitis and epiglottitis (P < or = 0.001) and more likely to have pneumonia and bacteremia (P < or = 0.001) than children with type b disease. For the last 2 years of the study invasive Hi disease occurring in a fully vaccinated child was more likely to be caused by a non-b strain than by a type b strain (58 vs. 38). In 1998 the incidence of non type-b Hi disease in all children <5 years of age in the UK was 1.3/100,000 as compared with an incidence of Hib disease of 0.6/100,000. The majority (88%) of non-b strains isolated in children were nontypable strains. CONCLUSIONS: Non-b Hi is a rare cause of disease in children, but in the Hib vaccine era it has become more common than type b as a cause of Hi disease in fully vaccinated children.

Behavioural risk factors among young adults in small areas with high mortality versus those in low-mortality areas.

A community-based cross-sectional survey of behavioural risk factors for premature mortality was carried out on a group of 354 adults aged 25-44 from previously identified high-mortality 'black-spots' in Dublin who were compared with 333 others from low-mortality areas. In the black-spot areas, 50.9% of respondents were current smokers versus 28.5% in low-mortality areas and 14.6% took 'sufficient' exercise versus 31.4% in low-mortality areas. People living in black spots were also less likely to make 'healthy' dietary choices than those in low-mortality areas. There is a higher prevalence of behavioural risk factors for premature mortality among young adults living in electoral wards/district electoral divisions (DEDs) with high standardized mortality ratios (SMRs) from all causes than among those in areas with low SMRs. A health promotion programme aimed at increasing exercise levels, reducing smoking and encouraging healthy eating should be aimed at young adults in DEDs with high SMRs.

Ten-year survival of Down syndrome births.

OBJECTIVE: To determine the survival status of children with Down syndrome (DS), and to document factors influencing survival. DESIGN: Follow-up study of cases identified from the Dublin European Register of Congenital Anomalies and Twins (EUROCAT) Register. Follow-up was attempted for each case until death or 1992 or until the date last known to be alive. SETTING: Eastern Health Board, Dublin. SUBJECTS: In all, 389 DS children, born between 1 January 1980 and 31 December 1989 were followed up. RESULTS: Survival rates of 88% at one year and 82% at 10 years were found. There was a non-significant improvement in survival between the cohort born in 1980-1984 and that born in 1985-1989. Congenital heart defects reduced survival to 72% and complete atrio-ventricular canal defects (CAVD) had the poorest prognosis (58% survival at 10 years). Cases with CAVD showed a trend towards improved survival when surgically treated. Maternal age mother's county of residence, sex of infant, season of birth and presence of additional non-cardiac congenital anomalies had no impact on survival. CONCLUSIONS: Four out of five DS children now survive at least 10 years. Adequate educational and health service provision needs to be made for them, especially those with congenital heart defects. The need for studies which compare survival and quality of life in DS children with CAVD who undergo cardiac surgery versus those who do not, taking account of various selection factors, is identified.

Intestinal mucosal mononuclear cell chimaerism after sex-mismatched allogeneic bone marrow transplantation.

The contribution of haemopoietic cell chimaerism to the pathogenesis of GVHD after BMT is unclear. This report raises the possibility that donor lymphocyte-recipient macrophage chimaerism may occur shortly after allogeneic marrow engraftment and hence might contribute to the development of GVHD. Immunohistological studies of intestinal mucosa in an allogeneic BMT patient, who did not engraft, revealed an almost complete absence of lymphocytes 30 days after transplant, but preservation of mucosal macrophage numbers. Subsequently, combined immunohistology-Y chromosome in situ hybridization studies were performed in two female BMT recipients of male donor marrow. These studies revealed that between 25 and 40% of macrophages and between 25 and 40% of T lymphocytes were of donor origin during the first 6 months after transplant. In conclusion, whilst the immunohistological studies of intestinal mucosa from a patient who failed to engraft suggest that donor lymphocyte-recipient macrophage ('split') chimaerism may occur shortly after marrow engraftment, the subsequent in situ hybridization studies revealed 'mixed' chimaerism in the two sex-mismatched BMT recipients.

Hepatitis B vaccine booster dose: low-dose recombinant hepatitis B vaccines as a booster dose.

BACKGROUND: The timing and best regimen for a booster dose of hepatitis B vaccine have not been determined. METHODS: Two studies were conducted to determine the response to a booster dose of 5 micrograms recombinant hepatitis B vaccine. In the first study, a 5 micrograms (0.5 ml) dose of Recombivax HB was administered intramuscularly 38 months after the initial dose to 71 volunteers. In a second study, we offered a 5 micrograms dose recombinant hepatitis B vaccine, either Recombivax HB (0.5 ml) or Engerix B (0.25 ml), to students who had previously been immunized with three doses of vaccine. RESULTS: In the first study, among the 44 persons for whom postbooster sera were available, the geometric mean concentration of anti-hepatitis B surface antigens increased from 42 to 2090 mIU/ml after the 5 micrograms (0.5 ml) dose of Recombivax. In the second study, after a 5 micrograms (0.5 ml) dose of Recombivax, the geometric mean concentration increased from 43 to 990 mIU/ml (n = 48), and in the group that received a 5 micrograms (0.25 ml) dose of Engerix B, the concentration increased from 83 to 2337 mIU/ml (n = 45) (p = 0.18 for postdose concentrations). CONCLUSION: A 5 micrograms dose of recombinant vaccine results in an excellent booster response at a cost one fourth to one half that of a full 1 ml dose of vaccine.

Advanced glycation end products in human penis: elevation in diabetic tissue, site of deposition, and possible effect through iNOS or eNOS.

OBJECTIVES: We hypothesized that advanced glycation end product (AGE) formation contributes to erectile dysfunction (ED) by quenching nitric oxide. Our first goal was to identify the specific AGE pentosidine in the diabetic human penis. Because AGE-mediated effects may involve inducible nitric oxide synthase (iNOS), we performed immunohistochemical and Western blot analysis of diabetic and nondiabetic human penile tissue for iNOS. Finally, because AGEs may act intracellularly to affect proteins, we set out to identify endothelial NOS (eNOS) in the human penis as an initial step in examining a possible intracellular interaction between eNOS and AGEs. METHODS: We performed high-performance liquid chromatographic analysis of diabetic human penile corpus cavernosum and serum for pentosidine and performed immunohistochemical, electron microscopic (EM), and Western blot analysis of the diabetic and nondiabetic penile corpus cavernosum and tunica for pyrraline, iNOS, and eNOS (and neural NOS [nNOS] for comparative purposes) via standard methods. RESULTS: We found a significant elevation of pentosidine in the penile tissue but not the serum of diabetic patients (average age 55.6 +/- 2.3 years) compared with that of nondiabetic patients (average age 61.8 +/- 3.6 years). Pentosidine was 117.06 +/- 9.19 pmol/mg collagen in the diabetic tunica versus 77.58 +/- 5.5 pmol/mg collagen in the nondiabetic tunica (P < 0.01) and 74.58 +/- 8.49 pmol/mg collagen in the diabetic corpus cavernosum versus 46.59 +/- 2.53 pmol/mg collagen in the nondiabetic corpus cavernosum (P < 0.01), suggesting a tissue-specific effect of the AGEs. We localized the site of deposition of the specific AGE pyrraline to the human penile tunica and the penile corpus cavernosum collagen. Immunohistochemical and EM analysis localized eNOS and iNOS to the cavernosal endothelium and smooth muscle. Western blot analysis in 6 patients revealed the following: iNOS, but no eNOS, in penile tissue from 1 insulin-dependent diabetic man; eNOS only in 1 man after radical prostatectomy; both eNOS and iNOS in 2 men with Peyronie's disease, as well as in 2 other men with impotence and hypertension. Finally, the specific iNOS inhibitor PNU-19451A significantly augmented relaxation of precontracted human cavernosal tissue, from 64.7% +/- 5.58 to 80.03% +/- 4.55 at 10 microM acetylcholine and 65.06% +/- 2.84 to 86.16% +/- 3.96 at 0.1 mM acetylcholine (n = 4, P < 0.002 and P < 0.02, respectively). CONCLUSIONS: AGEs are elevated in diabetic human penile tissue, but not in serum, and are localized to the collagen of the penile tunica and corpus cavernosum. We identified eNOS and iNOS in the human penile cavernosal smooth muscle and endothelium. The augmentation of cavernosal relaxation with a specific iNOS inhibitor, combined with the identification of iNOS protein, but not eNOS, in a patient with severe diabetes and ED, allows for speculation of a pathophysiologic mechanism for AGE-mediated ED via upregulation of iNOS and downregulation of eNOS. These data provide further insight into the mechanisms of advanced glycation end product-mediated ED and provide a foundation for further study.

GABA and benzodiazepine receptors in the cat motor thalamus after lesioning of nigro- and pallidothalamic pathways.

Binding parameters of [3H]muscimol ([3H]MUS) and [3H]flunitrazepam ([ 3H]FLU) were determined in the thalamic area of overlap of nigro- and pallidothalamic pathways at short- (1-10 weeks) and long-term (6-11 months) survival times after kainic acid lesioning of substantia nigra pairs reticularis (SNr) and/or entopeduncular nucleus (EPN). No statistically significant lesion-induced changes in Kd could be established in any of the lesioned groups. Bmax values for both binding sites, when corrected for nerve cell densities, revealed some changes in all but one instance (no statistically significant changes in the number of [3H]MUS binding sites were detected after SNr lesions). Significant bilateral increase in the number of [3H]MUS binding sites was found after unilateral EPN and combined EPN + SNr lesions. In the first group the changes were transient; in the second, the number of binding sites appeared to be still on the rise at 8 months postlesion. The latter increase was interpreted as resulting from plasticity type changes in GABAergic local circuit neurons in response to massive deafferentation from extrinsic inhibitory inputs. Changes in [3H]FLU binding sites were of different character and of extremely low magnitude compared to changes in [3H]MUS binding sites. Subtle, but statistically significant, ipsilateral increase in the number of [3H]FLU binding sites as a function of time postlesion was found in the SNr lesioned group. In two other lesioned groups small magnitude increase occurred bilaterally, although in the EPN lesioned group it was more pronounced on the operated side. The results are consistent with earlier suggestion that [3H]MUS and [3H]FLU binding sites in the motor thalamus appear to be associated with different types of GABAergic synapses with none of them being directly associated with the basal ganglia thalamic pathways.

Distribution and binding parameters of GABA and benzodiazepine receptors in the cat motor thalamus and adjacent nuclear groups.

Quantitative receptor binding autoradiography technique was utilized to study GABA and benzodiazepine receptors in the cat motor thalamus (ventral anterior, ventral medial and ventral lateral nuclei) and adjacent thalamic subdivisions. Binding parameters (Bmax and Kd) and distribution pattern of the binding sites for 3 tritiated ligands [3H]muscimol ([3H]MUS), [3H]flunitrazepam ([3H]FLU) and [3H]baclofen ([3H]BAC) were analyzed and compared using measurements from discrete and anatomically well-defined thalamic regions. There was little correlation in the regional distribution of the 3 binding sites. The concentration of [3H]BAC binding sites in thalamic nuclei of interest was very low, practically at the limit of resolution of the quantitative autoradiographic technique; whereas appreciable quantities of [3H]MUS and [3H]FLU binding sites were present in the motor and adjacent limbic nuclei of the thalamus. There was more difference between the nuclei in regard to the number of high affinity GABA receptors than benzodiazepine receptors. Moreover, the ratio of Bmax[3H]MUS/Bmax[3H]FLU varied from 2.2 to 4.4 in different thalamic regions suggesting the presence of a diverse population of GABAA and benzodiazepine receptors. The distribution pattern of the 3 binding sites was compared to the topography of GABAergic afferents of the basal ganglia origin and the frequency of GABAergic synapses formed by thalamic local circuit neurons (LCN) in the motor thalamus that were established earlier. It was concluded that in the cat motor thalamus: (1) none of the ligands studied appear to reveal the receptors associated with nigro- or pallidothalamic synapses; (2) [3H]MUS binding sites may be associated with the dendrodendritic contacts formed by LCN; and (3) the [3H]FLU binding sites are physically unrelated to [3H]MUS binding sites. The concentration of [3H]FLU and [3H]MUS binding sites in the midline nuclei and of [3H]MUS binding sites in the limbic nuclei was remarkably high. It was concluded that in addition to previously suggested limbic structures, the midline nuclei with their very high content of benzodiazepine receptors may be considered as a neuroanatomical substrate of certain forms of anxiety.

Porphyrin abnormalities in acquired immunodeficiency syndrome.

OBJECTIVE: To examine prospectively porphyrin metabolism in a human immunodeficiency virus (HIV)-positive population. SETTING: Specialist referral unit at the Department of Genitourinary Medicine, St James's Hospital, Dublin, Ireland. PATIENTS: Twenty-eight men and 5 women (age range, 18-35 years). Twenty-nine were current or previous intravenous drug abusers. Four were thought to have sexually acquired HIV infection. All had a history of acquired immunodeficiency syndrome-defining illnesses. The patients were selected as a consecutive sample from the inpatient department. Eligibility criteria were cooperation with urine and stool collection and confirmed HIV seropositivity. The patients were matched to 2 groups: 1 with normal results of porphyrin studies and the other with abnormal findings from porphyrin studies. INTERVENTION: None. MAIN OUTCOME MEASURES: Plasma, urine, and stool porphyrin excretion patterns. RESULTS: Of the 33 patients in the study, 13 (40%) had increased urinary porphyrin excretion. All but 2 of these patients were seropositive for hepatitis C virus. No study patient had clinical evidence of porphyria. Four patients (12%), however, had urine and stool porphyrin excretion patterns that were classic for porphyria cutanea tarda. All 4 of these patients were hepatitis C virus-positive. Patients with porphyrinuria had a greater degree of immunosuppression (P = .002) than those with normal porphyrin metabolism, and they were more likely to be taking zidovudine (P = .009). CONCLUSIONS: Commonly, porphyrin metabolism is abnormal in persons with established HIV infection. Hepatitis C may contribute to abnormal porphyrin metabolism. An unexpected number of patients studied had porphyrin excretion patterns that were characteristic of porphyria cutanea tarda, and all of these were hepatitis C virus-positive. A diagnosis of porphyria cutanea tarda, especially in a young patient, should prompt investigation for underlying HIV and hepatitis C virus infections. Dermatologists should be aware of the infectious risk associated with the vesicles and erosions in these patients. Porphyrin studies should be performed in any patient with HIV and photosensitivity.

Screening of patients with iron overload to identify hemochromatosis and porphyria cutanea tarda.

OBJECTIVE: To assess the importance of iron overload as a risk factor for porphyria cutanea tarda (PCT). DESIGN: Prospective study during a 4-month period. SETTING: Departments of emergency care, gastroenterology, and dermatology in a tertiary referral center. PATIENTS: Patients were deemed eligible for inclusion in the study if serum ferritin levels were greater than 500 micrograms/L (normal range: females, < 125 micrograms/L; males, < 325 micrograms/L). MAIN OUTCOME MEASURES: Porphyrin excretion profiles were analyzed on all patients included in the study, where clinically relevant. A diagnosis of PCT was confirmed biochemically in all cases. The HLA typing was then performed on newly diagnosed cases of PCT. RESULTS: Of 4127 patients tested, 240 patients with an elevated serum ferritin level were identified, of whom 74 had an elevated serum ferritin level of more than 500 micrograms/L. Of the latter group, 17.5% had hemochromatosis and 6.7% had PCT. The incidence of PCT in the hemochromatosis group was 23%; HLA typing revealed the presence of at least 1 of the hemochromatosis markers. CONCLUSIONS: A high serum ferritin level in the absence of evident cause should prompt investigation for both hemochromatosis and PCT. The HLA heterozygosity for hemochromatosis in some patients with PCT may be a cause of hepatic siderosis.

What did we learn about leadership in medical education? Effecting institutional change through the Interdisciplinary Generalist Curriculum Project.

The Interdisciplinary Generalist Curriculum (IGC) Project required significant collaboration and cooperation at many levels of leadership to accommodate early clinical experiences in the curriculum. Three elements of institutional change are discussed: the context for desired early clinical experiences in medical education, structural elements required of the IGC Project schools, and leadership within the demonstration schools. Lessons learned from these interdisciplinary projects include the importance of supportive leadership from the top levels, establishing broad buy-in across sectors of the school, creating a team administrative structure that fosters participation by all groups, and central (rather than departmental) administration. The processes needed to establish collaborative leadership and full participation by the generalist departments and cooperation of diverse constituencies, such as basic science faculty, were labor-intensive and required more time to ensure successful program implementation. Uniformly, strong support at the highest levels of the organization, especially the medical schools' deans, was cited as a key element in the success of the IGC Project. An interesting unanticipated outcome of the project was the movement of the interdisciplinary course administration into a central location (dean's office) by the end of the project for all schools. This change may reflect a practical advantage for administration of interdisciplinary programs located at the level of the school or college, rather than housed within departments.