HLA studies in a family with hereditary nephritis - abstract

In 1968, a four-year-old female (the index case) presented with post-streptococcal acute glomerulonephritis (PSAGN). A family visit was made and several members were found to have proteinuria and haematuria without evidence of PSAGN. This family was followed for over 20 years during which time six male members developed chronic renal disease (CRD). Three have since died and two of the three alive are now on dialysis. Mild proteinuria and/or haematuria has been found in other family members of the F and F 2 generations comprising 47 individuals. These observations led to the hypothesis that certain HLA antigens and/or haplotypes are associated with development of CRD in this family. HLA-A,B,C and DR typing were done on 25 available family members, 22 being absent for various reasons including migration. The studies revealed a homozygous condition for HLA-DR2 in the mother, resulting in the inheritance of DR2 in all siblings of the mother. Four of the five female offspring have been studied but only two have had proteinuria and haematuria. However, all male members of the f1 generation had copious proteinuria and three of the five studied had severe haematuria. More importantly, several members of the F 2 generation have already developed mild proteinuria and one female has severe haematuria though they are all clinically normal. Since it has been suggested that males of affected females tend to develop CRD, male offspring of the F 2 generation will be carefully monitored in future (AU)

Falciparum malaria treated with a chloroquine suspension administered rectally in Trinidad

A new mode of administering malaria chemotherapy to patients unable to tolerate oral medication is described. A patient with Plasmodium falciparum malaria, severe hyponatraemia and hypokalaemia who regurgitated oral treatment of chloroquine phosphate and pyrimethamine and sulfadoxine (Fansidar) is presented. But neither chloroquine nor quinine intravenous formulations were available locally. As the patient was deteriorating, a suspension of chloroquine phosphate was prepared and administered rectally, resulting in a decline in the level of parasitaemia from ++++ to ++ within 48 hours. The patient improved, and further clinical management was uncomplicated (AU)

Estimation of specific streptococcal antibodies from immune complexes in sera of patients with post-streptococcal acute glomerulonephritis - abstract

The enzyme-linked immunoabsorbent assay (ELISA) was used to determine the specific streptococcal antibodies in the sera of patients with post-streptococcal acute glomerulonephritis. Attempts to use this same technique to determine the immunoglobulin content of immune complexes (IC) after immunochemical dissociation proved futile. It became necessary to perform an inhibition assay before performing the ELISA. This modification involved the determination of the antigen concentration necessary to produce 50 per cent inhibition of the dissassociated antibody. The antigen inhibitors, M-types 41 and 55 cell membranes, were found to inhibit optimally at 12.5 ug/ml and were used to absorb dissassociated immune complexes diluted 1/00. The absorbed solution was then used in the ELISA test system. While specific streptococcal antibodies to M-55 were lower than those to M-41 (p<0.001) in PSAGN patients and those in controls (p<0.001), in the IC controls, specific antibodies to both inhibitors were of the same order. In PSAGN, however, the antibody levels were increased when compared with controls. Interestingly enough, specific streptococcal antibodies were demonstrated in IC of resolved GN cases, chronic GN and in those with intermittent proteinuria (AU)

A clinico-pathological study of yellow fever with demonstration of the virus in the human liver

The clinical histopathological and serological findings in three patients who developed yellow fever after entering the Guayaguayare forest in south-east Trinidad in January and February 1979 are described in this report. The patients were all previously healthy young males and the clinical features of the disease varied from fulminant viral hepatitis with hepato-renal failure to a self-limiting anicteric viral illness. The first patient died, and histopathological examination of the liver was done post-mortem. Needle biopsy of the liver was done on case 2 which presented with the clinical picture of infective hepatitis, and on case 3 with the features of an anicteric viral illness. The histopathological hallmarks of midzonal necrosis, granular eosinophilic degeneration (Councilman bodies) and fatty change in the parenchymal cells of the liver were seen in three cases. The electron microscopic study demonstrated the presence of the yellow fever virus in the liver of the patient who died.

A clinico-pathological study of yellow fever with demonstration of the virus in the human liver

The clinical histopathological and serological findings in three patients who developed yellow fever after entering the Guayaguayare forest in south-east Trinidad in January and February 1979 are described in this report. The patients were all previously healthy young males and the clinical features of the disease varied from fulminant viral hepatitis with hepato-renal failure to a self-limiting anicteric viral illness. The first patient died, and histopathological examination of the liver was done post-mortem. Needle biopsy of the liver was done on case 2 which presented with the clinical picture of infective hepatitis, and on case 3 with the features of an anicteric viral illness. The histopathological hallmarks of midzonal necrosis, granular eosinophilic degeneration (Councilman bodies) and fatty change in the parenchymal cells of the liver were seen in three cases. The electron microscopic study demonstrated the presence of the yellow fever virus in the liver of the patient who died (AU)

Genetic variation at the immunoglobulin allotype loci in Creoles of Trinidad

The sera of a sample of 204 Creoles from Trinidad were tested for the presence of polmorphic gene complexes occurring on immunoglobulin light and heavy-chain molecules including the allotypic markers IGKC 1, IGHA2 1 and 2, IGHG1 A, X, F, and Z, and IGHG3 G, G5, B0, B1, B3, B4, B5, C3, C5, S, and T. Nine IGHG (GM) haplotypes occur in polymorphic frequencies (greater than .01) in this population, including known African, Asian, Caucasian, and Amerindian marker haplotypes. Significant differences (P less than .01) were found in the frequency distributions of three IGHI (GM) haplotypes and the frequency of IGKC*1 in these data and data from Creole populations of Belize and St. Vincent. The Creoles of Trinidad and St. Vincent are more similar in IGHG (GM) haplotype distributions than are Trinidad and Belize populations. Previous testing has revealed no significant differences between St. Vincent and Belize Creoles at the Ig allotypic loci. Analysis of migration patterns in the Caribbean suggests that different rates of Asian migration have maintained regional diversity at these loci, while continuous gene flow from the eastern Caribbean to Trinidad has had a relative homogenising effect on the gene pools of this area. (AU)

Cellular immune responses and HLA antigens in post-streptococcal acute glomerulonephritis - abstract

Cellular immune reactions to non-specific mitogen, phytohaemagglutinin in (PHA) and specific blastogenic response to the nephritogenic strain, M55, of the streptococcus were investigated in an East Indian family in which all six siblings exhibited concurrent symptoms of post-streptococcal acute glomerulonephritis (PSAGN) requiring hospitalization. These assays, as well as HLA typing, were done on the entire family to determine whether a specific non-responder status to the M55 antigen was present in the family, and to investigate the possible presence of an immune response gene controlling M55 response. With the exception of one sibling, cellular immune reactions to PHA were similar to control responses, indicating normal overall T cell functions. Specific M55 stimulation revealed a decreased response (30 percent reduction relative to controls) in the cells of the father and 3 of the siblings. The results of HLA typing showed the presence of the B52/DR2 halotype in all siblings due to the homozygous presence of this halotype in the father. The B52 antigen was also present in the mother, resulting in a homozygous condition for this antigen in 4 of the 6 children. While it cannot be concluded from this single family study that the presence of B52 antigen is related to disease susceptibility, the repeated occurrence of this antigen, as well as the B52/DR2 halotype, in this family is noteworthy. The study further illustrates the usefulness of family studies in resolving apparent "blanks" which occur with some frequency in our small inbred island population (AU)

Epidemic scabies in four Caribbean islands, 1981-1988

Scabies infestation has been reported to the PAHO/WHO Caribbean Epidemiology Centre (CAREC) from Trinidad and Tobago (T&T), Grenada, Dominica, the Turks and Caicos islands (T&CI) and, more recently, St. Lucia. Epidemic scabies was being reported from T&CI in 1981 (1200/100000 population), but there were no reports from T&T until 1982 (8/100000). The first phase of the bimodal epidemic in Grenada ocurred between 1982 and 1984 (9132/100000) and the explosive second phase from 1985 to 1987 (474-699/100000). In T&T there was a low incidence of scabies until 1985 (0-59/1000000 and in Dominica the rate fluctuated (67-14/100000) during the same period. From 1986 to 1988, scabies infestation reached epidemic proportions in T&T (410-709/100000) and fluctuated in Dominica (108-117/100000). In Tobago alone, scabies was not reported until March 1986, and by December the incidence rate was 105/100000; by 1988 it had increased to 1124/100000 population. Although no secondary infections have been reported from Grenada, Dominica, T&CI or St. Lucia, T&T has reported increased streptococcal skin infections and epidemic post streptococcal skin infections and epidemic post-streptococcal acute glomerulonephritis (PSAGN). The observed trend of increasing scabies infestation, increasing streptococcal isolates from skin lesions, and increasing PSAGN in T&T is noteworthy. (AU)

New nephritogenic streptococcal serotypes during epidemic post-streptococcal acute glomerulonephritis - abstract

The increased incidence of reported scabies per 100,000 population from 24.2 in 1984 to 59.5 in 1985 led to a careful monitoring in 1986 of all patients with post-streptococcal acute glomerulonephritis (PSAGN). There were 18 cases of PSAGN, 72 of whom yield 84 streptococcal isolates, 65 of which belonged to group A. All streptococcal isolates were sent to the Central Public Health Laboratory Service, Colindale, England, for serotyping. The epidemic of PSAGN was bimodal, and the first phase (March to July) saw the advent of M-type 73 strain, one previously isolated 22 years ago by one of us (DCJB, unpublished data). Since then, there had been 2 subsequent isolates in 1978 and the reappearance of this strain appears to be associated with the first wave of the PSAGN epidemic. Another new strain, M-type 48, preceded the first phase of the epidemic and was isolated from 2 PSAGN patients. Provisional type (PT) 5757 had not previously been isolated in Trinidad. Seven patients yielded this strain which occurred during the first wave of the epidemic. Thus the first wave of the bimodal epidemic involved mainly the new serotypes M73, M48 and PT 5757 while the more intense second phase was associated mainly with M-type 55, a few of which also occurred during the first phase (AU)

Epidemic scabies in four Caribbean islands - abstract

Within the past seven years, scabies infestation has been reported to the PAHO/WHO Caribbean Epidemiology Centre from Trinidad and Tobago, Grenada, Dominica and the Turks and Caicos Islands. While epidemic scabies was reported from the Turks and Caicos Islands in 1981, this disease was absent from Trinidad and Tobago until 1982. Scabies infestation in Grenada appears to be bimodal, the first phase being between 1982 and 1984, and the explosive second phase from January 1985 to 1987. In Trinidad and Tobago, and in Dominica, there was a low incidence of scabies until 1986, when the infestation reached epidemic proportions. Although there have been no reports of secondary streptococcal infections from Grenada, Dominica or the Turks and Caicos Islands, Trinidad and Tobago has reported streptococcal infections and post-streptococcal acute glomerulonephritis (PSAGN). There is a trend of increasing scabies infestation, increasing streptococcal isolates from secondarily infected scabietic lesions, and increasing incidence of PSAGN in Trinidad. Almost certainly, a cost-benefit analysis of a scabies control programme would reveal a significant positive benefit-cost ratio. Other territories are encouraged to document the epidemiology of scabies to assist prevention and control (AU)

The importance of serum immunoglobulin levels and IgG subclass composition of circulating immune complexes in patients with post-streptococcal glomerulonephritis - abstract

Immunoglobulin levels, circulating immune complexes and IgG subclasses in the immune complexes were studied in sera from 34 patients with post-streptococcal acute glomerulonephritis (PSAGN). Serum IgG levels were depressed in 91 percent of PSAGN patients while serum IgA (82 percent) and IgM (97 percent) levels were elevated when compared with the mean values for 106 children all under 10 years of age. Circulating immune complexes were prepared by the 3 percent polyethylene glycol (PEG) 6,000 precipitation method and IgG- and IgM-containing immune complexes of PSAGN patients were elevated compared with those of controls. No IgA-containing complexes were seen in these patients. IgG-complexes returned to normal levels within 3-6 months after onset. In contrast, IgM-contain complexes, which were heightened at onset of illness, remained elevated even after six months. Subclass determinations of circulating IgG-containing immune complexes from PSAGN patients showed that IgGl and IgG2 were predominant while IgG3 was much reduced. IgGl-, IgG2- and IgG3- containing complexes returned to normal values within 3 months, but IgG2 complexes appeared to rise again at 6 months. IgG3-containing immune complexes appear to initiate glomerular injury in PSAGN patients whereas IgG2- containing immune complexes may be implicated in long-term glomerulonephritis (AU)

High dosage cyclophosphamide and dexamethasone treatment of paraquat poisoning with 75 percent survival

The mortality from paraquat poisoning is usually very high, and even in the best centres it exceeds 60 percent. In this paper, we report a treatment regimen with the surival of fifteen of twenty patients (75 percent) who had ingested 15 ml to 250ml of 20 percent and 24 percent paraquat. They were treated for 2 weeks with high doses of cyclophosphamide amd dexamethasone, forced diuresis with intravenous frusemide, triamterine and hydrochlorothiazide and liberal potassium supplements in addition to the routine measures for the elimination of paraquat from the gut with Fuller's Earth, activated charcoal and magnesium sulphate. The regimen is based on our hypothesis that the damage to the pulmonary alveolar capillary membrane is caused by superoxide produced by paraquat, and that this process triggers off further immunological changes with the activation of neutrophils and production of toxic oxygen metabolites by the immune complexes, and that the immunological mechanisms causing activation of the neutrophils are suppressed by cyclophosphamide and dexamethasone (AU)

Cyclophosphamide, dexamethasone and postassium in the treatment of paraquat poisoning - abstract

Paraquat, used extensively as a herbicide, is a potent human poison with a high mortality, 90 percent in our experience. As there is no antidote, treatment has been directed to rapid elimination from the body. Between July and November 1983, 8 of 11 cases were treated successfully using the regime reported in this paper. The diagnosis of paraquat poisoning was confirmed in all patients by the presence of oropharyngitis, positive test for paraquat in urine and evidence of renal and hepatic damage. Patients ingesting less than 5 ml, with negative tests for urinary paraquat on day 1-2, were excluded. Regime (1) Stomach washout followed by 60g of Fuller's Earth in 150 ml water, alternating with 10 tablets of activated charcoal 4-hourly for one week, oral fluids being encouraged. (2) Forced diuresis with frusemide 60 mg. stat followed by Dyazide (hydrochlorothiazide with triamterene) 1 tablet twice daily for one week, then one daily for one week. (3) Magnesium sulphate 15 ml. 8-hourly for one week. (4) Intravenous fluids (dextrosaline with added KC1 40 mEq/1) 4.31/d, for two weeks, followed by oral potassium, 8mEq 8-hourly for two weeks. (5) Intravenous dexamethasone 8 mg 8-hourly for two weeks, then 0.5mg. 8-hourly for two weeks. (6) Intravenous cyclophosphamide 5 mg/Kg to a total dose of 4 to 5 g. Treatment was started within 2 to 4 hours in all but three patients and all except for three had a stomach washout. The three fatalities were in males who ingested paraquat after taking rum. All died from mediastinitis following oesophageal rupture. All the survivors are well and have returned to normal activity with no evidence of residual hepatic, renal or pulmonary damage (AU)

Paraquat poisoning in South Trinidad 1972-1982

Self-poisoning is a major health problem in Trinidad. The changing pattern of self-poisoning between 1972 and 1982 was studied. Paraquat poisoning which was rare in 1972 reached epidemic proportions in 1982. The population at risk were young East Indians living in rural areas. In spite of the high morbidity and mortality associated with paraquat poisoning, this toxic herbicide is still easily available over the counter. Enforced legislation to control the sale of paraquat is urgently needed. (AU)

Paraquat as a cause of self-poisoning in South Trinidad: 1972 - 1982 - abstract

In 1974 we reported four (4) deaths from Paraquat poisoning in South Trinidad. The present study is an analysis of self-poisoning during a 16 month period from June 1981 to September 1982. Four hundred and thirty-five (435) cases of self poisoning were admitted to the San Fernando General Hospital during the period. Thirty-two (32) patients ingested "Tablets", -9 percent Paraquat, less than 1 percent organophosphorus insecticide and 58 percent a miscellaneous group of compounds. Admissions for self-poisoning have increased by 51 percent during the last 10 years. Paraquat poisoning which accounted for 1.3 percent in 1972 now accounts for 8.6 percent. Organophosphorus poisoning has decreased from 3.5 percent in 1972 to less than 1 percent in 1982. "Tablets" were the commonest ingested substance, both in 1972 (42 percent) and 1982 (32 percent). The morbidity and mortality from Paraquat continue to be high. Absorbents (Charcoal and Fuller's Earth), gastric lavage, whole gut lavage, and peritoneal dialysis were used in the treatment. In spite of intensive treatment mortality remains high (75 percent). The survivors usually ingested a small quantity and were treated aggressively. Deaths from self-poisoning in South Trinidad increased from 26 in 1972 to 57 in 1982. Of the 57 deaths at least 37 patients ingested Paraquat as compared to only 4 in 1972. Deaths from Paraquat poisoning were commonest among East Indian females living in rural areas. Our study highlights the increasing importance of Paraquat poisoning as a method of self-poisoning in Trinidad (AU)

Beta-Haemolytic group G. streptococci in Trinidad

During January to March, 1982, the throats of 175 apparently healthy school children, age range 5 - 11 years, were swabbed and examined for the presence of beta-haemolytic streptococci as a prerequisite to the determination of the immune response to streptococcal antigens in normal children.j There were 68 isolates comprising 39 belonging to Group A, 1 to Group B, 4 to Group C and 24 to Group G. This high rate of Group G colonisation was surprising. Subsequent examination of past record showed that of 114 throat swabs of apparently healthy school children taken in 1967, 36 yield streptococcal isolates of which 4 belonged to Group G. Of 199 cultures from skin lesions, 166 yielded streptococcal isolates of which 4 belonged to Group G but 2 of which were of mixed culture with Group A. These observations led to a review of cases of post streptococcal sequelae, acute rheumatic fever (ARF) and acute glomerulonephrotos (AGN) which occurred at the General Hospital, San Fernando, between January 1976 and July 1980 during which time all bacitracin positive streptococcal isolates from patients with post streptococcal sequelae were sent to the Public Health Laboratory, Colindale, England for grouping and typing. Of 1,073 isolates, 958 belonged to Group A, 18 to Group B, 19 to Group C, 5 to Group D and 63 to Group G. Of the 63 Group G isolates, one was isolated from the throat of a patient with ARF and 8 from siblings of ARF patients. More interestingly, there were 7 Group G isolates from skin lesions on patients with AGN and 47 from siblings of AGN patients. Though Group G streptococci have been associated with pharyngitis, neonatal sepsis and suspected gonococcal infections, this is the first report of a possible Group G associated post streptococcal acute glomerulonephritis (AU)

Congenital heart disease in the adult - abstract

This study is an analysis of eighty (80) cases of congenital heart disease seen in adults at the San Fernando General Hospital. This diagnosis was based on history, physical examination, chest X-Ray, electrocardiography, M-mode echocardiography, two-dimensional echocardiography and contrast two-dimensional echocardiography. Seventy per cent (70 percent) of the cases had septal defect, thirty-five per cent (35 percent) atrial and thirty-five per cent (35 percent) ventricular. Patent ductus arteriosus accounted for 12.5 per cent and cyanotic congenital heart disease 10 per cent. There were two cases of coarctation of the aorta, two of pulmonary stenosis and one each of aortic stenosis and anolamous pulmonary venous return. Females exceeded males by 2:1. Fifty-two per cent (52 percent) of the cases were in the age group 12 - 20 years and twenty-five per cent (25 percent) were older than age 30. Moderate to severe pulmonary hypertension was present in 23 cases - two patent ductus arteriosus, nine atrial septal defect and twelve ventricular septal defect. Shunt reversal was demonstrated with contrast two-dimensional echocardiography in five cases of ASD and six cases of ventricular septal defect. Two patients had corrective surgery - one closure of ASD at age 32 and the other repair of Fallot's tetralogy at age 17. After cardiac catherization two patients were considered inoperable because of severe pulmonary hypertension and poor ventricular function. Six patients died from congential heart disease. Three had trial septal defect with severe pulmonary hypertension, one each had ventricular septal defect, coarctation of the aorta and cyanotic congenital heart disease. The majority of our patients have defects which are surgically correctable with low mortality. The introduction of open-heart surgery in Trinidad in the near future should improve the prognosis of these patients (AU)