The Vancouver Lymphadenopathy-AIDS Study: 1. Persistent generalized lymphadenopathy

The Vancouver Lymphadenopathy-AIDS (acquired immune deficiency syndrome) Study is an ongoing prospective study of over 700 homosexual men attending six primary care practices in central Vancouver. A case-control study of risk factors for persistent generalized lymphadenopathy in homosexual men was conducted in five of the practices. The participants completed a questionnaire and underwent a complete physical examination at the time of enrolment and at a subsequent visit not less than 3 months later, and laboratory tests were performed after both visits. Persistent generalized lymphadenopathy was defined as the presence of lymph nodes greater than 1 cm in diameter at two or more extrainguinal sites for more than 3 months. Of the 519 patients who had completed both visits by February 1984, 126 (24%) were found to have the disease, and two controls without lymphadenopathy were frequencymatched on the basis of age and practice to each subject. More than 100 male sexual partners during one''s lifetime, frequent receptive anal intercourse, a history of gonorrhea, use of illicit drugs and sexual contact in Los Angeles were identified as independent risk factors for persistent generalized lymphadenopathy. The similarity of these risk factors to those established for AIDS supports the hypothesis of a common etiology for the two diseases, and the high prevalence rate of persistent generalized lymphadenopathy further supports the hypothesis that AIDS is an uncommon response to a relatively common agent.     

The Vancouver Lymphadenopathy-AIDS Study: 7. Clinical and laboratory features of 87 cases of primary HIV infection.

In an ongoing prospective study of homosexual men conducted in Vancouver since November 1982, 87 cases of human immunodeficiency virus (HIV) seroconversion have been documented to date. Comparison of laboratory results obtained a mean of 4.9 months before and 5.4 months after the estimated date of seroconversion revealed that a significant increase in the serum IgG level (from 1149 to 1335 mg/dl on average) and in C1q binding (from 8.8% to 14.2% on average) was associated with early HIV infection (p less than 0.001). A marginally significant decrease in the ratio of helper to suppressor (CD4 to CD8) cells (from 1.55 to 1.29 on average) was also noted (p = 0.025). A marked decrease in absolute number of CD4 cells was not seen with seroconversion, which suggests that profound loss of these cells may be a long-term effect of HIV infection. The occurrence of symptoms (including fatigue, fever, night sweats, unintentional weight loss, diarrhea, joint pains, cough unrelated to smoking, shortness of breath, oral thrush, herpes zoster and rash) did not increase with seroconversion. This finding suggests that most cases of HIV seroconversion may be asymptomatic or associated with relatively minor symptoms. On the other hand, generalized lymphadenopathy was found to develop after HIV seroconversion in about 50% of cases.     

The Vancouver Lymphadenopathy-AIDS Study: 3. Relation of HTLV-III seropositivity,immune status and lymphadenopathy.

In a study of 394 homosexual men recruited at the primary care level the prevalence of antibody to human T-lymphotropic retrovirus (HTLV-III) was higher among those with lymph node enlargement than among controls. The degree of abnormal immune function, as shown by abnormalities in immunoglobulin levels, immune complex activity and T-lymphocyte subsets, was correlated with the extent of lymphadenopathy. A similar pattern of immunologic abnormality was associated with seropositivity for HTLV-III antibody. However, HTLV-III seropositivity was the major determinant of immune function after adjustment for lymph node status. The results suggest that the immune dysfunction seen in patients with lymphadenopathy is due for the most part to the high prevalence of HTLV-III seropositivity in these populations. Lymphadenopathy, in many subjects, may in fact represent a physical sign of a stabilized compensated homeostatic host response. Factors responsible for severe immune decompensation associated with acquired immune deficiency syndrome (AIDS) may best be sought by prospective study of HTLV-III seropositive asymptomatic patients or those with stable persistent generalized lymphadenopathy and relatively normal immune function.     

The Vancouver Lymphadenopathy-AIDS Study: 4. Effects of exposure factors,cofactors and HTLV-III seropositivity on number of helper T cells.

Results of testing for antibody to human T-lymphotropic virus (HTLV-III) and absolute numbers of helper T cells in 219 participants in the Vancouver Lymphadenopathy-AIDS (acquired immune deficiency syndrome) Study were analysed. The mean absolute helper T-cell counts in the 141 HTLV-III seronegative and the 78 seropositive men were 897/mL and 659/mL respectively (p less than 0.001). Established AIDS risk factors such as elevated lifetime number of male sexual partners and frequent receptive anal intercourse did not appear to have any significant effect on number of helper T cells that was independent of HTLV-III antibody status. Seropositive men with less than 100, 100 to 500 or more than 500 male sexual partners in their lifetime had mean absolute helper T-cell counts of 667/mL, 651/mL and 662/mL respectively. Most other risk factors, as well, did not appear to exert any effect on absolute number of helper T cells that was independent of the effect of HTLV-III antibody status. However, independent effects of a history of mononucleosis or hepatitis and of cigarette smoking were noted. The data support the hypothesis that no immune dysfunction beyond that due to the initial infection alone arises from repeated exposure to HTLV-III. Most risk factors appear to act as exposure factors, exerting their effect on the immune system merely by increasing the probability of contact with the agent. The independent effects of a history of mononucleosis or hepatitis suggest that viral agents may be cofactors in the production of immune dysfunction.     

Toxic shock syndrome: clinical and laboratory findings in 30 patients.

Thirty patients with toxic shock syndrome (TSS) that developed between May 1980 and March 1983 in Vancouver were studied prospectively. In the 15 cases related to menstruation the illness followed a uniform and predictable clinical course. In the 15 other cases (3 in males) the disease was not related to menstruation, and the sources of the Staphylococcus aureus infections were diverse; 67% were hospital-acquired. Profound but transient lymphocytopenia associated with marked leukocytosis was the most striking laboratory finding and one not previously emphasized in the literature. S. aureus was isolated from sites of soft-tissue infection, the vagina or the endocervix in all except one case. Two patients had bacteremia. Phage types 29 and 29 + predominated among the isolates tested. All the genital S. aureus isolates tested produced the TSS marker protein, while the bacteria from wounds, throat, nose and blood were sometimes positive. Two patients (7%) died from refractory shock and multiple organ failure. All patients with a febrile, exanthematous, multisystem illness, particularly if it is associated with menstruation or a staphylococcal infection, should be evaluated promptly and treated empirically for TSS.     

The Vancouver Lymphadenopathy - AIDS Study: 2. Seroepidemiology of HTLV-III antibody

Testing for antibody to human T-lymphotropic retrovirus (HTLV-III) was carried out in 448 participants in the Vancouver Lymphadenopathy-AIDS (acquired immune deficiency syndrome) Study. The overall prevalence rate of seropositivity was 34%. Of 130 seronegative subjects followed for an average of 8.5 months, 14 became seropositive; thus, the approximate annual seroconversion rate was 15%. More than 100 male sexual partners in one''s lifetime, frequent receptive anal intercourse, fisting, a history of gonorrhea or hepatitis, and frequent sexual contact in clubs were found to be independent risk factors for HTLV-III seropositivity.     

Survival differences in European patients with AIDS, 1979-89. The AIDS in Europe Study Group.

OBJECTIVES--To examine the pattern of survival and factors associated with the outcome of disease in patients with AIDS. DESIGN--Inception cohort. Data collected retrospectively from patients'' charts. SETTING--52 clinical centres in 17 European countries. SUBJECTS--6578 adults diagnosed with AIDS from 1 January 1979 to 31 December 1989. MAIN OUTCOME MEASURES--Survival after the time of diagnosis. RESULTS--The median survival after diagnosis was 17 months, with an estimated survival at three years of 16% (95% confidence interval 15% to 17%). Patients diagnosed in southern Europe had a shorter survival, particularly immediately after the time of diagnosis, compared with patients diagnosed in central and northern Europe (survival at one year (95% confidence interval) 54% (52% to 56%) 66% (64% to 68%), 65% (63% to 66%), respectively. The three year survival, however, was similar for all regions. The regional differences in survival were less pronounced for patients diagnosed in 1989 compared with earlier years. Improved survival in recent years was observed for patients with a variety of manifestations used to define AIDS but was significant only for patients diagnosed with Pneumocystis carinii pneumonia. The three year survival, however, remains unchanged over time. CONCLUSIONS--Survival of AIDS patients seems to vary within Europe, being shorter in southern than central and northern Europe. The magnitude of these differences, however, has declined gradually over time. Short term survival has improved in recent years, but the long term prognosis has remained equally poor, reflecting the fact that the underlying infection with HIV and many of the complicating diseases remains essentially uncontrolled.     

The 48,XXYY syndrome. Follow-up data on clinical characteristics and psychological findings in 4 patients.

In this study we report the physical and psychological findings in 4 males with 48,XXYY syndrome. They were diagnosed at the ages of 4, 6, 18 and 25 years respectively. The major indication for chromosomal analysis in these four slightly mentally retarded males was not their clinical appearance but the presence of behavioral problems with personality disturbances i.e. psychotic reactions, loss of structure, violent and impulsive reactions. These data are compared with previous findings in the literature.     

Mutations, clinical findings and survival estimates in South American patients with X-linked adrenoleukodystrophy

In this study, we analyzed the ABCD1 gene in X-linked adrenoleukodystrophy (X-ALD) patients and relatives from 38 unrelated families from South America, as well as phenotypic proportions, survival estimates, and the potential effect of geographical origin in clinical characteristics.

Methods

X- ALD patients from Brazil, Argentina and Uruguay were invited to participate in molecular studies to determine their genetic status, characterize the mutations and improve the genetic counseling of their families. All samples were screened by SSCP analysis of PCR fragments, followed by automated DNA sequencing to establish the specific mutation in each family. Age at onset and at death, male phenotypes, genetic status of women, and the effect of family and of latitude of origin were also studied.

Results

We identified thirty-six different mutations (twelve novel). This population had an important allelic heterogeneity, as only p.Arg518Gln was repeatedly found (three families). Four cases carried de novo mutations. Intra-familiar phenotype variability was observed in all families. Out of 87 affected males identified, 65% had the cerebral phenotype (CALD). The mean (95% CI) ages at onset and at death of the CALD were 10.9 (9.1–12.7) and 24.7 (19.8–29.6) years. No association was found between phenotypic manifestations and latitude of origin. One index-case was a girl with CALD who carried an ABCD1 mutation, and had completely skewed X inactivation.

Conclusions

This study extends the spectrum of mutations in X-ALD, confirms the high rates of de novo mutations and the absence of common mutations, and suggests a possible high frequency of cerebral forms in our population.     

Histological, clinical and laboratory findings of acute exacerbation of Hashimoto's thyroiditis--comparison with those of subacute granulomatous thyroiditis

As reported previously, acute exacerbation of Hashimoto's thyroiditis shows quite unique histological findings, namely localized edematous inflammation. Similar histological characteristics and clinical manifestations were observed in 7 of 492 patients with Hashimoto's thyroiditis (A group). Their clinical and laboratory findings were compared with those of 15 cases with subacute granulomatous thyroiditis (S group). Age and sex distribution and goiters in A group were 39 +/- 21 years old (mean +/- s.d.), 7/0 (F/M), and 6/1 (diffuse/nodular), respectively. These were somewhat different from those of S group (45 +/- 9, 12/3, and 3/12, respectively). Thyroid functions in A group showed wide variation: 3 cases were euthyroid, 2 were mildly hypothyroid, and one was mildly thyrotoxic and one borderline thyrotoxic, and all of the S group patients were thyrotoxic. Their thyroid radiopertechnetate uptake, scintigraphy, duration from the onset till the first visit, and ESR and CRP values were also different from those of S group. Clinical courses and outcomes of A group were generally favorable, but one of them finally underwent a total thyroidectomy. Per os and intrathyroidal administrations of steroid were effective, but there was observed a recurrence of symptoms in 3 cases. Finally, all 6 cases were left with diffuse goiters, 4 of them remaining euthyroid, and 2 falling into hypothyroidism. The acute exacerbation of Hashimoto's thyroiditis is a rare complication, which is found to be different from subacute thyroiditis on histological, clinical and laboratory findings and is generally subtle. Steroid medication is considered to be the therapeutic choice but careful observation is necessary to avoid a recurrence.     

Virions associated with acute gastroenteritis in Vancouver, 1976.

Virions were identified by electron microscopic observation of unconcentrated extracts of feces obtained from 55 (33%) of 167 children aged 3 weeks to 5 years who were hospitalized with acute gastroenteritis at Children''s Hospital, Vancouver between January and December 1976. Morphologic types included 30 rotavirus, 15 adenovirus, 5 astrovirus and 5 picornavirus-like particles.     

AIDS and the general practitioner: views of patients with HIV infection and AIDS.

An unselected series of outpatients infected with the human immunodeficiency virus (HIV) who attended two London hospitals were interviewed to assess their relationship with their general practitioner. Although most of the 192 patients were registered with a general practitioner, the doctors of only one half knew of the diagnosis. Patients feared a negative reaction from their general practitioner or were concerned about confidentiality. Although those who had told their doctor had received favourable reactions, few general practitioners attempted to counsel or educate their patients. The patients who previously had been open about their homosexuality were not more likely to have told their general practitioner of their HIV infection. Although most did not think that general practitioners were well informed about AIDS, half of the patients wished that general practitioners could take a bigger part in their care.     

Cytogenetic and clinical findings in mares with gonadal dysgenesis.

Gonadal dysgenesis in the mare is associated with several different karyotypes, including sex chromosome aneuploidy (63,X; 63,X/64,XX; 63,X/64,XY or 65,XXX), the normal male complement (64,XY) and autosomal deletion (64,XX?del2q-). The 63,X is the most common karyotype found in gonadal dysgenesis. Aneuploid cases probably represent spontaneous chromosome non-disjunction during oogenesis, spermatogenesis or early embryonic development. Cases with XY or autosomal deletion may be inherited defects or of spontaneous origin.     

Human African trypanosomiasis with 7-year incubation period: Clinical,laboratory and neuroimaging findings

Human African trypanosomiasis (HAT), also referred to as “sleeping sickness”, is caused by the parasite Trypanosoma brucei. Diagnosing imported HAT outside endemic areas is difficult and diagnosis is often delayed. We report a case of imported human African trypanosomiasis caused by Trypanosoma brucei gambiense with an unusually long incubation period of at least 7 years. A 33 year old male African patient, a former resident of Cameroon, presented with a 4-month history of progressive personality changes. A few weeks before presentation the patient had first been admitted to a psychiatric ward and received antidepressant treatment, until a lumbar puncture showed pleocytosis and then antibiotic treatment for suspected neuroborreliosis was initiated. The patient continued to deteriorate during antibiotic treatment and became increasingly lethargic. Under antiparasitic and anti-inflammatory treatment, the condition of the patient gradually improved over the following months and he recovered completely after 24 months of follow-up. This well-documented case illustrates typical difficulties in establishing the correct diagnosis outside endemic areas and provides an overview of typical clinical, neuropathological and neuroimaging findings in T. b. gambiense trypanosomiasis, guiding the clinician in establishing the correct diagnosis in this rare disease.     

Methodological proposal in behavioural teratogenicity testing: assessment of propoxyphene, chlorpromazine, and vitamin A as positive controls

Pregnant Sprague-Dawley rats received either 80 mg/kg d-propoxyphene HCl or 20 mg/kg chlorpromazine HCl or 80,000 and 160,000 IU/kg vitamin A palmitate daily between the 6th and 20th days of gestation. Vehicle control groups were similarly treated with saline or corn oil and considered as negative controls. Offspring were examined for physical landmarks, neuromotor development, and behaviour using righting reflex, swimming, negative geotaxis, open field, rotarod, water maze, and nocturnal activity. This test battery included biochemical measurements. No reduction in parental weight and physical offspring development was observed. All these treatments produced long-term changes in more than one test. Vitamin A palmitate (160,000 IU/kg) was judged as the best positive control with this test battery for future investigation of the behavioural teratology of drugs.     

The role of hair in swimming of laboratory mice: implications for behavioural studies in animals with abnormal hair

Animal swimming tests, such as the forced swim test, are extensively used in biomedical research to study rodent behaviour. Hair and skin exposed to water may be an important factor affecting the performance in this test. Since various hair and skin abnormalities are not uncommon in genetically modified or drug-treated laboratory animals, this test may be inappropriate for these animals. Because on occasions it is necessary to screen their swimming behaviour, in the present study we aimed to assess the role of hair in swimming of laboratory rodents in the forced swim test, widely used in behavioural research. For this, we shaved laboratory mice (129S1 strain) and compared their swimming patterns with those of unshaven controls. Overall, shaving mice did not affect their swimming behaviours in the 5 min forced swim test. Our results indicate that hair condition is not an important factor in the forced swim test for this mouse strain, and suggest that this test may have wider utility for behavioural analyses of mice with abnormal hair.     

Clinical and laboratory findings in primary generalized and multiple-myeloma-related amyloidosis.

Thirty-four patients with primary generalized amyloidosis (PGA) and 14 with multiple-myeloma-related amyloidosis (MRA) were studied. The commonest clinical manifestations in PGA were nephrotic syndrome, hepatomegaly and congestive heart failure, and in MRA, low back pain, plasmacytoma and rheumatoid-arthritis-like syndrome. Eight patients with PGA had limited clinical expression of the disease, such as involvement of only kidneys, joints, parotid glands or gastrointestinal tract; in one patient amyloidosis was limited to lymph nodes. Low serum concentrations of total protein and albumin were common. M components were detected in the serum of 91% of patients with PGA and 92% of patients with MRA: 70% of the M components in PGA and 25% of those in MRA had lambda light chains. Bence Jones proteinemia was detected in 56% of the patients with PGA and in 77% of those with MRA. The serum concentration of immunoglobulins was decreased substantially in more than two thirds of the patients with PGA. Proteinuria (greater than 250 mg/24 h) was observed in 78% of patients with PGA and in 93% of patients with MRA. Bence Jones proteinuria was noted in 75 and 77% of patients, respectively. Plasmacytic infiltration of the bone marrow was found in 90% of the patients with PGA. The mean survival time of the patients with PGA was 28 months and of those with MRA, 29 months from the time of diagnosis.     

The epidemiological, clinical, and laboratory features of sporadic Creutzfeldt-Jakob disease patients in China: surveillance data from 2006 to 2010

Background

Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive fatal central nervous system disorder, which consists of three main catalogues: sporadic, familial, and iatrogenic CJD.

Methodology/Principal Findings

In China, the surveillance for CJD started in 2006, covering 12 provincial Centers for Disease Control and Prevention (CDCs) and 15 hospitals. From 2006 to 2010, 624 suspected patients were referred to China CJD surveillance. The epidemiological, clinical and laboratory features of sporadic CJD (sCJD) were analysed. Both groups of probable and possible sCJD showed highest incidences in the population of 60 to 69 year-olds. The most common presenting symptoms were progressive dementia and mental-related symptoms (neurological symptoms including sleeping turbulence, depression, anxiety and stress). Among the four main clinical manifestations, myoclonus was more frequently observed in the probable sCJD patients. About 2/3 of probable sCJD cases showed positive 14-3-3 in CSF and/or periodic sharp wave complexes (PSWC) in electroencephalography (EEG). The presence of myoclonus was significantly closely related with the appearance of PSWC in EEG. Polymorphisms of codon 129 in PRNP of the notified cases revealed a highly predominant M129M genotype in Han Chinese. Among 23 genetic human prion diseases, ten were D178N/M129M Fatal familial insomnia (FFI) and five were T188K genetic CJD (gCJD), possibly indicating a special distribution of gCJD-related mutations in Han Chinese.

Conclusion

From the period of 2006 to 2010, 261 patients were diagnosed as sCJD and 23 patients were diagnosed as genetic human prion diseases in China. The epidemiological, clinical and laboratory analysis data were consistent with the characteristics of sporadic CJD, which provide insight into the features of CJD in China.